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Sample records for variable specificity depending

  1. Eternity Variables to Simulate Specifications

    NARCIS (Netherlands)

    Hesselink, WH; Boiten, EA; Moller, B

    2002-01-01

    Simulation of specifications is introduced as a unification and generalization of refinement mappings, history variables, forward simulations, prophecy variables, and backward simulations. Eternity variables are introduced as a more powerful alternative for prophecy variables and backward

  2. Eternity Variables to Prove Simulation of Specifications

    NARCIS (Netherlands)

    Hesselink, Wim H.

    2005-01-01

    Simulations of specifications are introduced as a unification and generalization of refinement mappings, history variables, forward simulations, prophecy variables, and backward simulations. A specification implements another specification if and only if there is a simulation from the first one to

  3. Reward-dependent modulation of movement variability.

    Science.gov (United States)

    Pekny, Sarah E; Izawa, Jun; Shadmehr, Reza

    2015-03-04

    Movement variability is often considered an unwanted byproduct of a noisy nervous system. However, variability can signal a form of implicit exploration, indicating that the nervous system is intentionally varying the motor commands in search of actions that yield the greatest success. Here, we investigated the role of the human basal ganglia in controlling reward-dependent motor variability as measured by trial-to-trial changes in performance during a reaching task. We designed an experiment in which the only performance feedback was success or failure and quantified how reach variability was modulated as a function of the probability of reward. In healthy controls, reach variability increased as the probability of reward decreased. Control of variability depended on the history of past rewards, with the largest trial-to-trial changes occurring immediately after an unrewarded trial. In contrast, in participants with Parkinson's disease, a known example of basal ganglia dysfunction, reward was a poor modulator of variability; that is, the patients showed an impaired ability to increase variability in response to decreases in the probability of reward. This was despite the fact that, after rewarded trials, reach variability in the patients was comparable to healthy controls. In summary, we found that movement variability is partially a form of exploration driven by the recent history of rewards. When the function of the human basal ganglia is compromised, the reward-dependent control of movement variability is impaired, particularly affecting the ability to increase variability after unsuccessful outcomes. Copyright © 2015 the authors 0270-6474/15/354015-10$15.00/0.

  4. Problems Identifying Independent and Dependent Variables

    Science.gov (United States)

    Leatham, Keith R.

    2012-01-01

    This paper discusses one step from the scientific method--that of identifying independent and dependent variables--from both scientific and mathematical perspectives. It begins by analyzing an episode from a middle school mathematics classroom that illustrates the need for students and teachers alike to develop a robust understanding of…

  5. Benford's law and continuous dependent random variables

    Science.gov (United States)

    Becker, Thealexa; Burt, David; Corcoran, Taylor C.; Greaves-Tunnell, Alec; Iafrate, Joseph R.; Jing, Joy; Miller, Steven J.; Porfilio, Jaclyn D.; Ronan, Ryan; Samranvedhya, Jirapat; Strauch, Frederick W.; Talbut, Blaine

    2018-01-01

    Many mathematical, man-made and natural systems exhibit a leading-digit bias, where a first digit (base 10) of 1 occurs not 11% of the time, as one would expect if all digits were equally likely, but rather 30%. This phenomenon is known as Benford's Law. Analyzing which datasets adhere to Benford's Law and how quickly Benford behavior sets in are the two most important problems in the field. Most previous work studied systems of independent random variables, and relied on the independence in their analyses. Inspired by natural processes such as particle decay, we study the dependent random variables that emerge from models of decomposition of conserved quantities. We prove that in many instances the distribution of lengths of the resulting pieces converges to Benford behavior as the number of divisions grow, and give several conjectures for other fragmentation processes. The main difficulty is that the resulting random variables are dependent. We handle this by using tools from Fourier analysis and irrationality exponents to obtain quantified convergence rates as well as introducing and developing techniques to measure and control the dependencies. The construction of these tools is one of the major motivations of this work, as our approach can be applied to many other dependent systems. As an example, we show that the n ! entries in the determinant expansions of n × n matrices with entries independently drawn from nice random variables converges to Benford's Law.

  6. Trait-specific dependence in romantic relationships.

    Science.gov (United States)

    Ellis, Bruce J; Simpson, Jeffry A; Campbell, Lorne

    2002-10-01

    Informed by three theoretical frameworks--trait psychology, evolutionary psychology, and interdependence theory--we report four investigations designed to develop and test the reliability and validity of a new construct and accompanying multiscale inventory, the Trait-Specific Dependence Inventory (TSDI). The TSDI assesses comparisons between present and alternative romantic partners on major dimensions of mate value. In Study 1, principal components analyses revealed that the provisional pool of theory-generated TSDI items were represented by six factors: Agreeable/Committed, Resource Accruing Potential, Physical Prowess, Emotional Stability, Surgency, and Physical Attractiveness. In Study 2, confirmatory factor analysis replicated these results on a different sample and tested how well different structural models fit the data. Study 3 provided evidence for the convergent and discriminant validity of the six TSDI scales by correlating each one with a matched personality trait scale that did not explicitly incorporate comparisons between partners. Study 4 provided further validation evidence, revealing that the six TSDI scales successfully predicted three relationship outcome measures--love, time investment, and anger/upset--above and beyond matched sets of traditional personality trait measures. These results suggest that the TSDI is a reliable, valid, and unique construct that represents a new trait-specific method of assessing dependence in romantic relationships. The construct of trait-specific dependence is introduced and linked with other theories of mate value.

  7. Reduction in camera-specific variability in [{sup 123}I]FP-CIT SPECT outcome measures by image reconstruction optimized for multisite settings: impact on age-dependence of the specific binding ratio in the ENC-DAT database of healthy controls

    Energy Technology Data Exchange (ETDEWEB)

    Buchert, Ralph; Lange, Catharina [Charite - Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Kluge, Andreas; Bronzel, Marcus [ABX-CRO advanced pharmaceutical services Forschungsgesellschaft m.b.H., Dresden (Germany); Tossici-Bolt, Livia [University Hospital Southampton NHS Foundation Trust, Department of Medical Physics, Southampton (United Kingdom); Dickson, John [University College London Hospital NHS Foundation Trust, Institute of Nuclear Medicine, London (United Kingdom); Asenbaum, Susanne [Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, L. Oezlem Atay [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Svarer, Claus [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Koulibaly, Pierre-Malick [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Department of Neuroscience (DINOGMI), Clinical Neurology Unit, Genoa (Italy); Pagani, Marco [CNR, Institute of Cognitive Sciences and Technologies, Rome (Italy); Karolinska Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Tatsch, Klaus [Municipal Hospital of Karlsruhe Inc, Department of Nuclear Medicine, Karlsruhe (Germany); Borght, Thierry vander [CHU Namur, IREC, Nuclear Medicine Division, Universite catholique de Louvain, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Varrone, Andrea [Karolinska University Hospital, Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm (Sweden); Iida, Hidehiro [National Cerebral and Cardiovascular Center - Research Institute, Osaka (Japan)

    2016-07-15

    Quantitative estimates of dopamine transporter availability, determined with [{sup 123}I]FP-CIT SPECT, depend on the SPECT equipment, including both hardware and (reconstruction) software, which limits their use in multicentre research and clinical routine. This study tested a dedicated reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [{sup 123}I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis. Of 73 healthy subjects from the European Normal Control Database of [{sup 123}I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration by transmission-dependent convolution subtraction, iterative OSEM reconstruction including attenuation correction, and camera-specific ''to kBq/ml'' calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [{sup 123}I]FP-CIT binding ratio (SBR) was computed using the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure. The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2) with whole brain as the reference, independently of the reconstruction algorithm. QSPECT reconstruction appears to be useful for reduction of camera-specific intersubject variability of [{sup 123}I]FP-CIT SPECT in multisite and single-site multicamera settings. Whole brain excluding striatal binding as the reference provides more stable quantitative estimates than occipital or cerebellar binding. (orig.)

  8. Age dependant somatometric and cephalometric variables among ...

    African Journals Online (AJOL)

    Background: The process of growth passes through stages of developmental processes. This stage is the age. Age is known to affect many parameters in the body and this includes somatometric and cephalometric variables. Methods: The study was conducted with a total number of 409 students of university of Jos, ...

  9. Maximal Inequalities for Dependent Random Variables

    DEFF Research Database (Denmark)

    Hoffmann-Jorgensen, Jorgen

    2016-01-01

    Maximal inequalities play a crucial role in many probabilistic limit theorem; for instance, the law of large numbers, the law of the iterated logarithm, the martingale limit theorem and the central limit theorem. Let X-1, X-2,... be random variables with partial sums S-k = X-1 + ... + X-k. Then a......Maximal inequalities play a crucial role in many probabilistic limit theorem; for instance, the law of large numbers, the law of the iterated logarithm, the martingale limit theorem and the central limit theorem. Let X-1, X-2,... be random variables with partial sums S-k = X-1 + ... + X......-k. Then a maximal inequality gives conditions ensuring that the maximal partial sum M-n = max(1) (...

  10. Future-dependent Flow Policies with Prophetic Variables

    DEFF Research Database (Denmark)

    Li, Ximeng; Nielson, Flemming; Nielson, Hanne Riis

    2016-01-01

    future-dependent flow policies- policies that can depend on not only the current values of variables, but also their final values. The final values are referred to using what we call prophetic variables, just as the initial values can be referenced using logical variables in Hoare logic. We develop...... and enforce a notion of future-dependent security for open systems, in the spirit of "non-deducibility on strategies". We also illustrate our approach in scenarios where future-dependency has advantages over present-dependency and avoids mixtures of upgradings and downgradings....

  11. Validity of a Residualized Dependent Variable after Pretest Covariance Adjustments: Still the Same Variable?

    Science.gov (United States)

    Nimon, Kim; Henson, Robin K.

    2015-01-01

    The authors empirically examined whether the validity of a residualized dependent variable after covariance adjustment is comparable to that of the original variable of interest. When variance of a dependent variable is removed as a result of one or more covariates, the residual variance may not reflect the same meaning. Using the pretest-posttest…

  12. Fixed transaction costs and modelling limited dependent variables

    NARCIS (Netherlands)

    Hempenius, A.L.

    1994-01-01

    As an alternative to the Tobit model, for vectors of limited dependent variables, I suggest a model, which follows from explicitly using fixed costs, if appropriate of course, in the utility function of the decision-maker.

  13. Hoeffding’s Inequality for Sums of Dependent Random Variables

    Czech Academy of Sciences Publication Activity Database

    Pelekis, Christos; Ramon, J.

    2017-01-01

    Roč. 14, č. 6 (2017), č. článku 243. ISSN 1660-5446 Institutional support: RVO:67985807 Keywords : dependent random variables * Hoeffding’s inequality * k-wise independent random variables * martingale differences Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.868, year: 2016

  14. Statistical Dependence of Pipe Breaks on Explanatory Variables

    Directory of Open Access Journals (Sweden)

    Patricia Gómez-Martínez

    2017-02-01

    Full Text Available Aging infrastructure is the main challenge currently faced by water suppliers. Estimation of assets lifetime requires reliable criteria to plan assets repair and renewal strategies. To do so, pipe break prediction is one of the most important inputs. This paper analyzes the statistical dependence of pipe breaks on explanatory variables, determining their optimal combination and quantifying their influence on failure prediction accuracy. A large set of registered data from Madrid water supply network, managed by Canal de Isabel II, has been filtered, classified and studied. Several statistical Bayesian models have been built and validated from the available information with a technique that combines reference periods of time as well as geographical location. Statistical models of increasing complexity are built from zero up to five explanatory variables following two approaches: a set of independent variables or a combination of two joint variables plus an additional number of independent variables. With the aim of finding the variable combination that provides the most accurate prediction, models are compared following an objective validation procedure based on the model skill to predict the number of pipe breaks in a large set of geographical locations. As expected, model performance improves as the number of explanatory variables increases. However, the rate of improvement is not constant. Performance metrics improve significantly up to three variables, but the tendency is softened for higher order models, especially in trunk mains where performance is reduced. Slight differences are found between trunk mains and distribution lines when selecting the most influent variables and models.

  15. How a dependent's variable non-randomness affects taper equation ...

    African Journals Online (AJOL)

    In order to apply the least squares method in regression analysis, the values of the dependent variable Y should be random. In an example of regression analysis linear and nonlinear taper equations, which estimate the diameter of the tree dhi at any height of the tree hi, were compared. For each tree the diameter at the ...

  16. Daily affect variability and context-specific alcohol consumption.

    Science.gov (United States)

    Mohr, Cynthia D; Arpin, Sarah; McCabe, Cameron T

    2015-11-01

    Research explored the effects of variability in negative and positive affect on alcohol consumption, specifying daily fluctuation in affect as a critical form of emotion dysregulation. Using daily process methodology allows for a more objective calculation of affect variability relative to traditional self-reports. The present study models within-person negative and positive affect variabilities as predictors of context-specific consumption (i.e. solitary vs. social drinking), controlling for mean levels of affect. A community sample of moderate-to-heavy drinkers (n = 47; 49% women) from a US metropolitan area reported on affect and alcohol consumption thrice daily for 30 days via a handheld electronic interviewer. Within-person affect variability was calculated using daily standard deviations in positive and negative affect. Within person, greater negative and positive variabilities are related to greater daily solitary and social consumption. Across study days, mean levels of negative and positive affect variabilities related to greater social consumption between persons; yet, aggregated negative affect variability was related to less solitary consumption. Results affirm affect variability as a unique predictor of alcohol consumption, independent of mean affect levels. Yet, it is important to differentiate social context of consumption, as well as type of affect variability, particularly at the between-person level. These distinctions help clarify inconsistencies in the self-medication literature regarding associations between average levels of affect and consumption. Importantly, consistent within-person relationships for both variabilities support arguments that both negative and positive affect variabilities are detrimental and reflect an inability to regulate emotional experience. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  17. The discovery of timescale-dependent color variability of quasars

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yu-Han; Wang, Jun-Xian; Chen, Xiao-Yang [CAS Key Laboratory for Research in Galaxies and Cosmology, Department of Astronomy, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zheng, Zhen-Ya, E-mail: sunyh92@mail.ustc.edu.cn, E-mail: jxw@ustc.edu.cn [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85287 (United States)

    2014-09-01

    Quasars are variable on timescales from days to years in UV/optical and generally appear bluer while they brighten. The physics behind the variations in fluxes and colors remains unclear. Using Sloan Digital Sky Survey g- and r-band photometric monitoring data for quasars in Stripe 82, we find that although the flux variation amplitude increases with timescale, the color variability exhibits the opposite behavior. The color variability of quasars is prominent at timescales as short as ∼10 days, but gradually reduces toward timescales up to years. In other words, the variable emission at shorter timescales is bluer than that at longer timescales. This timescale dependence is clearly and consistently detected at all redshifts from z = 0 to 3.5; thus, it cannot be due to contamination to broadband photometry from emission lines that do not respond to fast continuum variations. The discovery directly rules out the possibility that simply attributes the color variability to contamination from a non-variable redder component such as the host galaxy. It cannot be interpreted as changes in global accretion rate either. The thermal accretion disk fluctuation model is favored in the sense that fluctuations in the inner, hotter region of the disk are responsible for short-term variations, while longer-term and stronger variations are expected from the larger and cooler disk region. An interesting implication is that one can use quasar variations at different timescales to probe disk emission at different radii.

  18. Brain noise is task dependent and region specific.

    Science.gov (United States)

    Misić, Bratislav; Mills, Travis; Taylor, Margot J; McIntosh, Anthony R

    2010-11-01

    The emerging organization of anatomical and functional connections during human brain development is thought to facilitate global integration of information. Recent empirical and computational studies have shown that this enhanced capacity for information processing enables a diversified dynamic repertoire that manifests in neural activity as irregularity and noise. However, transient functional networks unfold over multiple time, scales and the embedding of a particular region depends not only on development, but also on the manner in which sensory and cognitive systems are engaged. Here we show that noise is a facet of neural activity that is also sensitive to the task context and is highly region specific. Children (6-16 yr) and adults (20-41 yr) performed a one-back face recognition task with inverted and upright faces. Neuromagnetic activity was estimated at several hundred sources in the brain by applying a beamforming technique to the magnetoencephalogram (MEG). During development, neural activity became more variable across the whole brain, with most robust increases in medial parietal regions, such as the precuneus and posterior cingulate cortex. For young children and adults, activity evoked by upright faces was more variable and noisy compared with inverted faces, and this effect was reliable only in the right fusiform gyrus. These results are consistent with the notion that upright faces engender a variety of integrative neural computations, such as the relations among facial features and their holistic constitution. This study shows that transient changes in functional integration modulated by task demand are evident in the variability of regional neural activity.

  19. Quadratic time dependent Hamiltonians and separation of variables

    International Nuclear Information System (INIS)

    Anzaldo-Meneses, A.

    2017-01-01

    Time dependent quantum problems defined by quadratic Hamiltonians are solved using canonical transformations. The Green’s function is obtained and a comparison with the classical Hamilton–Jacobi method leads to important geometrical insights like exterior differential systems, Monge cones and time dependent Gaussian metrics. The Wei–Norman approach is applied using unitary transformations defined in terms of generators of the associated Lie groups, here the semi-direct product of the Heisenberg group and the symplectic group. A new explicit relation for the unitary transformations is given in terms of a finite product of elementary transformations. The sequential application of adequate sets of unitary transformations leads naturally to a new separation of variables method for time dependent Hamiltonians, which is shown to be related to the Inönü–Wigner contraction of Lie groups. The new method allows also a better understanding of interacting particles or coupled modes and opens an alternative way to analyze topological phases in driven systems. - Highlights: • Exact unitary transformation reducing time dependent quadratic quantum Hamiltonian to zero. • New separation of variables method and simultaneous uncoupling of modes. • Explicit examples of transformations for one to four dimensional problems. • New general evolution equation for quadratic form in the action, respectively Green’s function.

  20. Quadratic time dependent Hamiltonians and separation of variables

    Science.gov (United States)

    Anzaldo-Meneses, A.

    2017-06-01

    Time dependent quantum problems defined by quadratic Hamiltonians are solved using canonical transformations. The Green's function is obtained and a comparison with the classical Hamilton-Jacobi method leads to important geometrical insights like exterior differential systems, Monge cones and time dependent Gaussian metrics. The Wei-Norman approach is applied using unitary transformations defined in terms of generators of the associated Lie groups, here the semi-direct product of the Heisenberg group and the symplectic group. A new explicit relation for the unitary transformations is given in terms of a finite product of elementary transformations. The sequential application of adequate sets of unitary transformations leads naturally to a new separation of variables method for time dependent Hamiltonians, which is shown to be related to the Inönü-Wigner contraction of Lie groups. The new method allows also a better understanding of interacting particles or coupled modes and opens an alternative way to analyze topological phases in driven systems.

  1. Incorporation of gene-specific variability improves expression analysis using high-density DNA microarrays

    Directory of Open Access Journals (Sweden)

    Spitznagel Edward

    2003-11-01

    Full Text Available Abstract Background The assessment of data reproducibility is essential for application of microarray technology to exploration of biological pathways and disease states. Technical variability in data analysis largely depends on signal intensity. Within that context, the reproducibility of individual probe sets has not been hitherto addressed. Results We used an extraordinarily large replicate data set derived from human placental trophoblast to analyze probe-specific contribution to variability of gene expression. We found that signal variability, in addition to being signal-intensity dependant, is probe set-specific. Importantly, we developed a novel method to quantify the contribution of this probe set-specific variability. Furthermore, we devised a formula that incorporates a priori-computed, replicate-based information on probe set- and intensity-specific variability in determination of expression changes even without technical replicates. Conclusion The strategy of incorporating probe set-specific variability is superior to analysis based on arbitrary fold-change thresholds. We recommend its incorporation to any computation of gene expression changes using high-density DNA microarrays. A Java application implementing our T-score is available at http://www.sadovsky.wustl.edu/tscore.html.

  2. Panel data models extended to spatial error autocorrelation or a spatially lagged dependent variable

    NARCIS (Netherlands)

    Elhorst, J. Paul

    2001-01-01

    This paper surveys panel data models extended to spatial error autocorrelation or a spatially lagged dependent variable. In particular, it focuses on the specification and estimation of four panel data models commonly used in applied research: the fixed effects model, the random effects model, the

  3. Dependent leaders : Role-specific challenges for middle managers

    NARCIS (Netherlands)

    Voorn, Bart

    2018-01-01

    Mocked and ridiculed by many, praised by few, middle managers have challenging roles in organizations. It is typified by unique dependencies on different aspects of their work circumstances, including their superiors’ leadership, assigned goals, and tenure. Empirical research exploring specific

  4. Exercise training improves heart rate variability after methamphetamine dependency.

    Science.gov (United States)

    Dolezal, Brett Andrew; Chudzynski, Joy; Dickerson, Daniel; Mooney, Larissa; Rawson, Richard A; Garfinkel, Alan; Cooper, Christopher B

    2014-06-01

    Heart rate variability (HRV) reflects a healthy autonomic nervous system and is increased with physical training. Methamphetamine dependence (MD) causes autonomic dysfunction and diminished HRV. We compared recently abstinent methamphetamine-dependent participants with age-matched, drug-free controls (DF) and also investigated whether HRV can be improved with exercise training in the methamphetamine-dependent participants. In 50 participants (MD = 28; DF = 22), resting heart rate (HR; R-R intervals) was recorded over 5 min while seated using a monitor affixed to a chest strap. Previously reported time domain (SDNN, RMSSD, pNN50) and frequency domain (LFnu, HFnu, LF/HF) parameters of HRV were calculated with customized software. MD were randomized to thrice-weekly exercise training (ME = 14) or equal attention without training (MC = 14) over 8 wk. Groups were compared using paired and unpaired t-tests. Statistical significance was set at P ≤ 0.05. Participant characteristics were matched between groups (mean ± SD): age = 33 ± 6 yr; body mass = 82.7 ± 12 kg, body mass index = 26.8 ± 4.1 kg·min. Compared with DF, the MD group had significantly higher resting HR (P HRV indices were similar between ME and MC groups. However, after training, the ME group significantly (all P HRV, based on several conventional indices, was diminished in recently abstinent, methamphetamine-dependent individuals. Moreover, physical training yielded a marked increase in HRV, representing increased vagal modulation or improved autonomic balance.

  5. Value of Construction Company and its Dependence on Significant Variables

    Science.gov (United States)

    Vítková, E.; Hromádka, V.; Ondrušková, E.

    2017-10-01

    The paper deals with the value of the construction company assessment respecting usable approaches and determinable variables. The reasons of the value of the construction company assessment are different, but the most important reasons are the sale or the purchase of the company, the liquidation of the company, the fusion of the company with another subject or the others. According the reason of the value assessment it is possible to determine theoretically different approaches for valuation, mainly it concerns about the yield method of valuation and the proprietary method of valuation. Both approaches are dependant of detailed input variables, which quality will influence the final assessment of the company´s value. The main objective of the paper is to suggest, according to the analysis, possible ways of input variables, mainly in the form of expected cash-flows or the profit, determination. The paper is focused mainly on methods of time series analysis, regression analysis and mathematical simulation utilization. As the output, the results of the analysis on the case study will be demonstrated.

  6. Country-Specific Effects of Climate Variability on Human Migration

    Science.gov (United States)

    Gray, Clark; Wise, Erika

    2016-01-01

    Involuntary human migration is among the social outcomes of greatest concern in the current era of global climate change. Responding to this concern, a growing number of studies have investigated the consequences of short to medium-term climate variability for human migration using demographic and econometric approaches. These studies have provided important insights, but at the same time have been significantly limited by lack of expertise in the use of climate data, access to cross-national data on migration, and attention to model specification. To address these limitations, we link data on internal and international migration over a 6-year period from 9,812 origin households in Kenya, Uganda, Nigeria, Burkina Faso and Senegal to high-resolution gridded climate data from both station and satellite sources. Analyses of these data using several plausible specifications reveal that climate variability has country-specific effects on migration: Migration tends to increase with temperature anomalies in Uganda, tends to decrease with temperature anomalies in Kenya and Burkina Faso, and shows no consistent relationship with temperature in Nigeria and Senegal. Consistent with previous studies, precipitation shows weak and inconsistent relationships with migration across countries. These results challenge generalizing narratives that foresee a consistent migratory response to climate change across the globe. PMID:27092012

  7. Country-Specific Effects of Climate Variability on Human Migration.

    Science.gov (United States)

    Gray, Clark; Wise, Erika

    2016-04-01

    Involuntary human migration is among the social outcomes of greatest concern in the current era of global climate change. Responding to this concern, a growing number of studies have investigated the consequences of short to medium-term climate variability for human migration using demographic and econometric approaches. These studies have provided important insights, but at the same time have been significantly limited by lack of expertise in the use of climate data, access to cross-national data on migration, and attention to model specification. To address these limitations, we link data on internal and international migration over a 6-year period from 9,812 origin households in Kenya, Uganda, Nigeria, Burkina Faso and Senegal to high-resolution gridded climate data from both station and satellite sources. Analyses of these data using several plausible specifications reveal that climate variability has country-specific effects on migration: Migration tends to increase with temperature anomalies in Uganda, tends to decrease with temperature anomalies in Kenya and Burkina Faso, and shows no consistent relationship with temperature in Nigeria and Senegal. Consistent with previous studies, precipitation shows weak and inconsistent relationships with migration across countries. These results challenge generalizing narratives that foresee a consistent migratory response to climate change across the globe.

  8. Using k-dependence causal forest to mine the most significant dependency relationships among clinical variables for thyroid disease diagnosis.

    Directory of Open Access Journals (Sweden)

    LiMin Wang

    Full Text Available Numerous data mining models have been proposed to construct computer-aided medical expert systems. Bayesian network classifiers (BNCs are more distinct and understandable than other models. To graphically describe the dependency relationships among clinical variables for thyroid disease diagnosis and ensure the rationality of the diagnosis results, the proposed k-dependence causal forest (KCF model generates a series of submodels in the framework of maximum spanning tree (MST and demonstrates stronger dependence representation. Friedman test on 12 UCI datasets shows that KCF has classification accuracy advantage over the other state-of-the-art BNCs, such as Naive Bayes, tree augmented Naive Bayes, and k-dependence Bayesian classifier. Our extensive experimental comparison on 4 medical datasets also proves the feasibility and effectiveness of KCF in terms of sensitivity and specificity.

  9. A study of variable thrust, variable specific impulse trajectories for solar system exploration

    Science.gov (United States)

    Sakai, Tadashi

    A study has been performed to determine the advantages and disadvantages of variable thrust and variable Isp (specific impulse) trajectories for solar system exploration. There have been several numerical research efforts for variable thrust, variable Isp, power-limited trajectory optimization problems. All of these results conclude that variable thrust, variable Isp (variable specific impulse, or VSI) engines are superior to constant thrust, constant Isp (constant specific impulse; or CSI) engines. However, most of these research efforts assume a mission from Earth to Mars, and some of them further assume that these planets are circular and coplanar. Hence they still lack the generality. This research has been conducted to answer the following questions: (1) Is a VSI engine always better than a CSI engine or a high thrust engine for any mission to any planet with any time of flight considering lower propellant mass as the sole criterion? (2) If a planetary swing-by is used for a VSI trajectory, is the fuel savings of a VSI swing-by trajectory better than that of a CSI swing-by or high thrust swing-by trajectory? To support this research, an unique, new computer-based interplanetary trajectory calculation program has been created. This program utilizes a calculus of variations algorithm to perform overall optimization of thrust, Isp, and thrust vector direction along a trajectory that minimizes fuel consumption for interplanetary travel. It is assumed that the propulsion system is power-limited, and thus the compromise between thrust and Isp is a variable to be optimized along the flight path. This program is capable of optimizing not only variable thrust trajectories but also constant thrust trajectories in 3-D space using a planetary ephemeris database. It is also capable of conducting planetary swing-bys. Using this program, various Earth-originating trajectories have been investigated and the optimized results have been compared to traditional CSI and high

  10. Fluctuation-dissipation theorem for frequency-dependent specific heat

    DEFF Research Database (Denmark)

    Dyre, Jeppe; Nielsen, Johannes K.

    1996-01-01

    A derivation of the fluctuation-dissipation (FD) theorem for the frequency-dependent specific heat of a system described by a master equation is presented. The FD theorem is illustrated by a number of simple examples, including a system described by a linear Langevin equation, a two-level system......, and a system described by the energy master equation. It is shown that for two quite different models with low-energy cutoffs—a collection of two-level systems and a system described by the energy master equation—the frequency-dependent specific heat in dimensionless units becomes universal at low temperatures......, i.e., independent of both energy distribution and temperature. These two models give almost the same universal frequency-dependent specific heat, which compares favorably to experiments on supercooled alcohols....

  11. Motivation as an independent and a dependent variable in medical education: a review of the literature.

    Science.gov (United States)

    Kusurkar, R A; Ten Cate, Th J; van Asperen, M; Croiset, G

    2011-01-01

    Motivation in learning behaviour and education is well-researched in general education, but less in medical education. To answer two research questions, 'How has the literature studied motivation as either an independent or dependent variable? How is motivation useful in predicting and understanding processes and outcomes in medical education?' in the light of the Self-determination Theory (SDT) of motivation. A literature search performed using the PubMed, PsycINFO and ERIC databases resulted in 460 articles. The inclusion criteria were empirical research, specific measurement of motivation and qualitative research studies which had well-designed methodology. Only studies related to medical students/school were included. Findings of 56 articles were included in the review. Motivation as an independent variable appears to affect learning and study behaviour, academic performance, choice of medicine and specialty within medicine and intention to continue medical study. Motivation as a dependent variable appears to be affected by age, gender, ethnicity, socioeconomic status, personality, year of medical curriculum and teacher and peer support, all of which cannot be manipulated by medical educators. Motivation is also affected by factors that can be influenced, among which are, autonomy, competence and relatedness, which have been described as the basic psychological needs important for intrinsic motivation according to SDT. Motivation is an independent variable in medical education influencing important outcomes and is also a dependent variable influenced by autonomy, competence and relatedness. This review finds some evidence in support of the validity of SDT in medical education.

  12. Human phoneme recognition depending on speech-intrinsic variability.

    Science.gov (United States)

    Meyer, Bernd T; Jürgens, Tim; Wesker, Thorsten; Brand, Thomas; Kollmeier, Birger

    2010-11-01

    The influence of different sources of speech-intrinsic variation (speaking rate, effort, style and dialect or accent) on human speech perception was investigated. In listening experiments with 16 listeners, confusions of consonant-vowel-consonant (CVC) and vowel-consonant-vowel (VCV) sounds in speech-weighted noise were analyzed. Experiments were based on the OLLO logatome speech database, which was designed for a man-machine comparison. It contains utterances spoken by 50 speakers from five dialect/accent regions and covers several intrinsic variations. By comparing results depending on intrinsic and extrinsic variations (i.e., different levels of masking noise), the degradation induced by variabilities can be expressed in terms of the SNR. The spectral level distance between the respective speech segment and the long-term spectrum of the masking noise was found to be a good predictor for recognition rates, while phoneme confusions were influenced by the distance to spectrally close phonemes. An analysis based on transmitted information of articulatory features showed that voicing and manner of articulation are comparatively robust cues in the presence of intrinsic variations, whereas the coding of place is more degraded. The database and detailed results have been made available for comparisons between human speech recognition (HSR) and automatic speech recognizers (ASR).

  13. Specification and Verification of Context-dependent Services

    Directory of Open Access Journals (Sweden)

    Naseem Ibrahim

    2011-08-01

    Full Text Available Current approaches for the discovery, specification, and provision of services ignore the relationship between the service contract and the conditions in which the service can guarantee its contract. Moreover, they do not use formal methods for specifying services, contracts, and compositions. Without a formal basis it is not possible to justify through formal verification the correctness conditions for service compositions and the satisfaction of contractual obligations in service provisions. We remedy this situation in this paper. We present a formal definition of services with context-dependent contracts. We define a composition theory of services with context-dependent contracts taking into consideration functional, nonfunctional, legal and contextual information. Finally, we present a formal verification approach that transforms the formal specification of service composition into extended timed automata that can be verified using the model checking tool UPPAAL.

  14. Variability of interconnected wind plants: correlation length and its dependence on variability time scale

    Science.gov (United States)

    St. Martin, Clara M.; Lundquist, Julie K.; Handschy, Mark A.

    2015-04-01

    The variability in wind-generated electricity complicates the integration of this electricity into the electrical grid. This challenge steepens as the percentage of renewably-generated electricity on the grid grows, but variability can be reduced by exploiting geographic diversity: correlations between wind farms decrease as the separation between wind farms increases. But how far is far enough to reduce variability? Grid management requires balancing production on various timescales, and so consideration of correlations reflective of those timescales can guide the appropriate spatial scales of geographic diversity grid integration. To answer ‘how far is far enough,’ we investigate the universal behavior of geographic diversity by exploring wind-speed correlations using three extensive datasets spanning continents, durations and time resolution. First, one year of five-minute wind power generation data from 29 wind farms span 1270 km across Southeastern Australia (Australian Energy Market Operator). Second, 45 years of hourly 10 m wind-speeds from 117 stations span 5000 km across Canada (National Climate Data Archive of Environment Canada). Finally, four years of five-minute wind-speeds from 14 meteorological towers span 350 km of the Northwestern US (Bonneville Power Administration). After removing diurnal cycles and seasonal trends from all datasets, we investigate dependence of correlation length on time scale by digitally high-pass filtering the data on 0.25-2000 h timescales and calculating correlations between sites for each high-pass filter cut-off. Correlations fall to zero with increasing station separation distance, but the characteristic correlation length varies with the high-pass filter applied: the higher the cut-off frequency, the smaller the station separation required to achieve de-correlation. Remarkable similarities between these three datasets reveal behavior that, if universal, could be particularly useful for grid management. For high

  15. Solute transport modelling with the variable temporally dependent ...

    Indian Academy of Sciences (India)

    Pintu Das

    2018-02-07

    Feb 7, 2018 ... in a finite domain with time-dependent sources and dis- tance-dependent dispersivities. Also, existing ... solute transport in multi-layered porous media using gen- eralized integral transform technique with .... methods for solving the fractional reaction-–sub-diffusion equation. To solve numerically the Eqs.

  16. ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

    Science.gov (United States)

    Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

    2006-12-01

    The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

  17. On Direction of Dependence in Latent Variable Contexts

    Science.gov (United States)

    von Eye, Alexander; Wiedermann, Wolfgang

    2014-01-01

    Approaches to determining direction of dependence in nonexperimental data are based on the relation between higher-than second-order moments on one side and correlation and regression models on the other. These approaches have experienced rapid development and are being applied in contexts such as research on partner violence, attention deficit…

  18. Mesencephalic basolateral domain specification is dependent on Sonic Hedgehog

    Science.gov (United States)

    Martinez-Lopez, Jesus E.; Moreno-Bravo, Juan A.; Madrigal, M. Pilar; Martinez, Salvador; Puelles, Eduardo

    2015-01-01

    In the study of central nervous system morphogenesis, the identification of new molecular markers allows us to identify domains along the antero-posterior and dorso-ventral (DV) axes. In the past years, the alar and basal plates of the midbrain have been divided into different domains. The precise location of the alar-basal boundary is still under discussion. We have identified Barhl1, Nhlh1 and Six3 as appropriate molecular markers to the adjacent domains of this transition. The description of their expression patterns and the contribution to the different mesencephalic populations corroborated their role in the specification of these domains. We studied the influence of Sonic Hedgehog on these markers and therefore on the specification of these territories. The lack of this morphogen produced severe alterations in the expression pattern of Barhl1 and Nhlh1 with consequent misspecification of the basolateral (BL) domain. Six3 expression was apparently unaffected, however its distribution changed leading to altered basal domains. In this study we confirmed the localization of the alar-basal boundary dorsal to the BL domain and demonstrated that the development of the BL domain highly depends on Shh. PMID:25741244

  19. Mesencephalic basolateral domain specification is dependent on Sonic Hedgehog

    Directory of Open Access Journals (Sweden)

    Jesus E. Martinez-Lopez

    2015-02-01

    Full Text Available In the study of central nervous system morphogenesis, the identification of new molecular markers allows us to identify domains along the antero-posterior and dorso-ventral axes. In the past years, the alar and basal plates of the midbrain have been divided into different domains. The precise location of the alar-basal boundary is still under discussion. We have identified Barhl1, Nhlh1 and Six3 as appropriate molecular markers to the adjacent domains of this transition. The description of their expression patterns and the contribution to the different mesencephalic populations corroborated their role in the specification of these domains. We studied the influence of Sonic Hedgehog on these markers and therefore on the specification of these territories. The lack of this morphogen produced severe alterations in the expression pattern of Barhl1 and Nhlh1 with consequent misspecification of the basolateral domain. Six3 expression was apparently unaffected, however its distribution changed leading to altered basal domains. In this study we confirmed the localization of the alar-basal boundary dorsal to the basolateral domain and demonstrated that the development of the basolateral domain highly depends on Shh.

  20. Total Variability Modeling using Source-specific Priors

    DEFF Research Database (Denmark)

    Shepstone, Sven Ewan; Lee, Kong Aik; Li, Haizhou

    2016-01-01

    sequence of an utterance. In both cases the prior for the latent variable is assumed to be non-informative, since for homogeneous datasets there is no gain in generality in using an informative prior. This work shows in the heterogeneous case, that using informative priors for com- puting the posterior......, can lead to favorable results. We focus on modeling the priors using minimum divergence criterion or fac- tor analysis techniques. Tests on the NIST 2008 and 2010 Speaker Recognition Evaluation (SRE) dataset show that our proposed method beats four baselines: For i-vector extraction using an already...... trained matrix, for the short2-short3 task in SRE’08, five out of eight female and four out of eight male common conditions, were improved. For the core-extended task in SRE’10, four out of nine female and six out of nine male common conditions were improved. When incorporating prior information...

  1. Cannabis-related hippocampal volumetric abnormalities specific to subregions in dependent users.

    Science.gov (United States)

    Chye, Yann; Suo, Chao; Yücel, Murat; den Ouden, Lauren; Solowij, Nadia; Lorenzetti, Valentina

    2017-07-01

    Cannabis use is associated with neuroanatomical alterations in the hippocampus. While the hippocampus is composed of multiple subregions, their differential vulnerability to cannabis dependence remains unknown. The objective of the study is to investigate gray matter alteration in each of the hippocampal subregions (presubiculum, subiculum, cornu ammonis (CA) subfields CA1-4, and dentate gyrus (DG)) as associated with cannabis use and dependence. A total of 35 healthy controls (HC), 22 non-dependent (CB-nondep), and 39 dependent (CB-dep) cannabis users were recruited. We investigated group differences in hippocampal subregion volumes between HC, CB-nondep, and CB-dep users. We further explored the association between CB use variables (age of onset of regular use, monthly use, lifetime use) and hippocampal subregions in CB-nondep and CB-dep users separately. The CA1, CA2/3, CA4/DG, as well as total hippocampal gray matter were reduced in volume in CB-dep but not in CB-nondep users, relative to HC. The right CA2/3 and CA4/DG volumes were also negatively associated with lifetime cannabis use in CB-dep users. Our results suggest a regionally and dependence-specific influence of cannabis use on the hippocampus. Hippocampal alteration in cannabis users was specific to the CA and DG regions and confined to dependent users.

  2. Sex-specific selection for MHC variability in Alpine chamois

    Directory of Open Access Journals (Sweden)

    Schaschl Helmut

    2012-02-01

    Full Text Available Abstract Background In mammals, males typically have shorter lives than females. This difference is thought to be due to behavioural traits which enhance competitive abilities, and hence male reproductive success, but impair survival. Furthermore, in many species males usually show higher parasite burden than females. Consequently, the intensity of selection for genetic factors which reduce susceptibility to pathogens may differ between sexes. High variability at the major histocompatibility complex (MHC genes is believed to be advantageous for detecting and combating the range of infectious agents present in the environment. Increased heterozygosity at these immune genes is expected to be important for individual longevity. However, whether males in natural populations benefit more from MHC heterozygosity than females has rarely been investigated. We investigated this question in a long-term study of free-living Alpine chamois (Rupicapra rupicapra, a polygynous mountain ungulate. Results Here we show that male chamois survive significantly (P = 0.022 longer if heterozygous at the MHC class II DRB locus, whereas females do not. Improved survival of males was not a result of heterozygote advantage per se, as background heterozygosity (estimated across twelve microsatellite loci did not change significantly with age. Furthermore, reproductively active males depleted their body fat reserves earlier than females leading to significantly impaired survival rates in this sex (P Conclusions Increased MHC class II DRB heterozygosity with age in males, suggests that MHC heterozygous males survive longer than homozygotes. Reproductively active males appear to be less likely to survive than females most likely because of the energetic challenge of the winter rut, accompanied by earlier depletion of their body fat stores, and a generally higher parasite burden. This scenario renders the MHC-mediated immune response more important for males than for females

  3. Unsteady Flow in a Supersonic Turbine with Variable Specific Heats

    Science.gov (United States)

    Dorney, Daniel J.; Griffin, Lisa W.; Huber, Frank; Sondak, Douglas L.; Turner, James (Technical Monitor)

    2001-01-01

    Modern high-work turbines can be compact, transonic, supersonic, counter-rotating, or use a dense drive gas. The vast majority of modern rocket turbine designs fall into these Categories. These turbines usually have large temperature variations across a given stage, and are characterized by large amounts of flow unsteadiness. The flow unsteadiness can have a major impact on the turbine performance and durability. For example, the Space Transportation Main Engine (STME) fuel turbine, a high work, transonic design, was found to have an unsteady inter-row shock which reduced efficiency by 2 points and increased dynamic loading by 24 percent. The Revolutionary Reusable Technology Turbopump (RRTT), which uses full flow oxygen for its drive gas, was found to shed vortices with such energy as to raise serious blade durability concerns. In both cases, the sources of the problems were uncovered (before turbopump testing) with the application of validated, unsteady computational fluid dynamics (CFD) to the designs. In the case of the RRTT and the Alternate Turbopump Development (ATD) turbines, the unsteady CFD codes have been used not just to identify problems, but to guide designs which mitigate problems due to unsteadiness. Using unsteady flow analyses as a part of the design process has led to turbine designs with higher performance (which affects temperature and mass flow rate) and fewer dynamics problems. One of the many assumptions made during the design and analysis of supersonic turbine stages is that the values of the specific heats are constant. In some analyses the value is based on an average of the expected upstream and downstream temperatures. In stages where the temperature can vary by 300 to 500 K, however, the assumption of constant fluid properties may lead to erroneous performance and durability predictions. In this study the suitability of assuming constant specific heats has been investigated by performing three-dimensional unsteady Navier

  4. Energy decay of a variable-coefficient wave equation with nonlinear time-dependent localized damping

    Directory of Open Access Journals (Sweden)

    Jieqiong Wu

    2015-09-01

    Full Text Available We study the energy decay for the Cauchy problem of the wave equation with nonlinear time-dependent and space-dependent damping. The damping is localized in a bounded domain and near infinity, and the principal part of the wave equation has a variable-coefficient. We apply the multiplier method for variable-coefficient equations, and obtain an energy decay that depends on the property of the coefficient of the damping term.

  5. Microenvironment Dependent Photobiomodulation on Function-Specific Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Timon Cheng-Yi Liu

    2014-01-01

    Full Text Available Cellular photobiomodulation on a cellular function has been shown to be homeostatic. Its function-specific pathway mechanism would be further discussed in this paper. The signal transduction pathways maintaining a normal function in its function-specific homeostasis (FSH, resisting the activation of many other irrelative signal transduction pathways, are so sparse that it can be supposed that there may be normal function-specific signal transduction pathways (NSPs. A low level laser irradiation or monochromatic light may promote the activation of partially activated NSP and/or its redundant NSP so that it may induce the second-order phase transition of a function from its dysfunctional one far from its FSH to its normal one in a function-specific microenvironment and may also induce the first-order functional phase transition of the normal function from low level to high level.

  6. Motormouth: Mere Exposure Depends on Stimulus-Specific Motor Simulations

    Science.gov (United States)

    Topolinski, Sascha; Strack, Fritz

    2009-01-01

    The authors apply an embodied account to mere exposure, arguing that through the repeated exposure of a particular stimulus, motor responses specifically associated to that stimulus are repeatedly simulated, thus trained, and become increasingly fluent. This increased fluency drives preferences for repeated stimuli. This hypothesis was tested by…

  7. Non-uniform approximations for sums of discrete m-dependent random variables

    OpenAIRE

    Vellaisamy, P.; Cekanavicius, V.

    2013-01-01

    Non-uniform estimates are obtained for Poisson, compound Poisson, translated Poisson, negative binomial and binomial approximations to sums of of m-dependent integer-valued random variables. Estimates for Wasserstein metric also follow easily from our results. The results are then exemplified by the approximation of Poisson binomial distribution, 2-runs and $m$-dependent $(k_1,k_2)$-events.

  8. Frictional Heating with Time-Dependent Specific Power of Friction

    Directory of Open Access Journals (Sweden)

    Topczewska Katarzyna

    2017-06-01

    Full Text Available In this paper analytical solutions of the thermal problems of friction were received. The appropriate boundary-value problems of heat conduction were formulated and solved for a homogeneous semi–space (a brake disc heated on its free surface by frictional heat fluxes with different and time-dependent intensities. Solutions were obtained in dimensionless form using Duhamel's theorem. Based on received solutions, evolution and spatial distribution of the dimensionless temperature were analyzed using numerical methods. The numerical results allowed to determine influence of the time distribution of friction power on the spatio-temporal temperature distribution in brake disc.

  9. The Attentional Dependence of Emotion Cognition is Variable with the Competing Task

    Directory of Open Access Journals (Sweden)

    Cheng Chen

    2016-11-01

    Full Text Available The relationship between emotion and attention has fascinated researchers for decades. Many previous studies have used eye-tracking, ERP, MEG and fMRI to explore this issue but have reached different conclusions: some researchers hold that emotion cognition is an automatic process and independent of attention, while some others believed that emotion cognition is modulated by attentional resources and is a type of controlled processing. The present research aimed to investigate this controversy, and we hypothesized that the attentional dependence of emotion cognition is variable with the competing task. Eye-tracking technology and a dual-task paradigm were adopted, and subjects’ attention was manipulated to fixate at the central task to investigate whether subjects could detect the emotional faces presented in the peripheral area with a decrease or near-absence of attention. The results revealed that when the peripheral task was emotional face discrimination but the central attention-demanding task was different, subjects performed well in the peripheral task, which means that emotional information can be processed in parallel with other stimuli, and there may be a specific channel in the human brain for processing emotional information. However, when the central and peripheral tasks were both emotional face discrimination, subjects could not perform well in the peripheral task, indicating that the processing of emotional information required attentional resources and that it is a type of controlled processing. Therefore, we concluded that the attentional dependence of emotion cognition varied with the competing task.

  10. Incorporating residual temperature and specific humidity in predicting weather-dependent warm-season electricity consumption

    Science.gov (United States)

    Guan, Huade; Beecham, Simon; Xu, Hanqiu; Ingleton, Greg

    2017-02-01

    Climate warming and increasing variability challenges the electricity supply in warm seasons. A good quantitative representation of the relationship between warm-season electricity consumption and weather condition provides necessary information for long-term electricity planning and short-term electricity management. In this study, an extended version of cooling degree days (ECDD) is proposed for better characterisation of this relationship. The ECDD includes temperature, residual temperature and specific humidity effects. The residual temperature is introduced for the first time to reflect the building thermal inertia effect on electricity consumption. The study is based on the electricity consumption data of four multiple-street city blocks and three office buildings. It is found that the residual temperature effect is about 20% of the current-day temperature effect at the block scale, and increases with a large variation at the building scale. Investigation of this residual temperature effect provides insight to the influence of building designs and structures on electricity consumption. The specific humidity effect appears to be more important at the building scale than at the block scale. A building with high energy performance does not necessarily have low specific humidity dependence. The new ECDD better reflects the weather dependence of electricity consumption than the conventional CDD method.

  11. Heritability of specific language impairment depends on diagnostic criteria.

    Science.gov (United States)

    Bishop, D V M; Hayiou-Thomas, M E

    2008-04-01

    Heritability estimates for specific language impairment (SLI) have been inconsistent. Four twin studies reported heritability of 0.5 or more, but a recent report from the Twins Early Development Study found negligible genetic influence in 4-year-olds. We considered whether the method of ascertainment influenced results and found substantially higher heritability if SLI was defined in terms of referral to speech and language pathology services than if defined by language test scores. Further analysis showed that presence of speech difficulties played a major role in determining whether a child had contact with services. Childhood language disorders that are identified by population screening are likely to have a different phenotype and different etiology from clinically referred cases. Genetic studies are more likely to find high heritability if they focus on cases who have speech difficulties and who have been referred for intervention.

  12. Site-specific variability of loess and palaeosols (Ruma, Vojvodina, northern Serbia)

    NARCIS (Netherlands)

    Vandenberghe, J.; Markovic, S.B.; Jovanovic, M.; Hambach, U.

    2013-01-01

    The study of temporal variations in soil intensity has mostly been limited to specific sites. However, it is important for correctly interpreting the stratigraphy and palaeoclimatic significance of loess and palaeosols series to understand the reasons for the spatial variability. More specifically,

  13. Punishment induced behavioural and neurophysiological variability reveals dopamine-dependent selection of kinematic movement parameters

    Science.gov (United States)

    Galea, Joseph M.; Ruge, Diane; Buijink, Arthur; Bestmann, Sven; Rothwell, John C.

    2013-01-01

    Action selection describes the high-level process which selects between competing movements. In animals, behavioural variability is critical for the motor exploration required to select the action which optimizes reward and minimizes cost/punishment, and is guided by dopamine (DA). The aim of this study was to test in humans whether low-level movement parameters are affected by punishment and reward in ways similar to high-level action selection. Moreover, we addressed the proposed dependence of behavioural and neurophysiological variability on DA, and whether this may underpin the exploration of kinematic parameters. Participants performed an out-and-back index finger movement and were instructed that monetary reward and punishment were based on its maximal acceleration (MA). In fact, the feedback was not contingent on the participant’s behaviour but pre-determined. Blocks highly-biased towards punishment were associated with increased MA variability relative to blocks with either reward or without feedback. This increase in behavioural variability was positively correlated with neurophysiological variability, as measured by changes in cortico-spinal excitability with transcranial magnetic stimulation over the primary motor cortex. Following the administration of a DA-antagonist, the variability associated with punishment diminished and the correlation between behavioural and neurophysiological variability no longer existed. Similar changes in variability were not observed when participants executed a pre-determined MA, nor did DA influence resting neurophysiological variability. Thus, under conditions of punishment, DA-dependent processes influence the selection of low-level movement parameters. We propose that the enhanced behavioural variability reflects the exploration of kinematic parameters for less punishing, or conversely more rewarding, outcomes. PMID:23447607

  14. Equivalent conditions of complete moment convergence for extended negatively dependent random variables

    Directory of Open Access Journals (Sweden)

    Qunying Wu

    2017-05-01

    Full Text Available Abstract In this paper, we study the equivalent conditions of complete moment convergence for sequences of identically distributed extended negatively dependent random variables. As a result, we extend and generalize some results of complete moment convergence obtained by Chow (Bull. Inst. Math. Acad. Sin. 16:177-201, 1988 and Li and Spătaru (J. Theor. Probab. 18:933-947, 2005 from the i.i.d. case to extended negatively dependent sequences.

  15. Nanostructures study of CNT nanofluids transport with temperature-dependent variable viscosity in a muscular tube

    Science.gov (United States)

    Akbar, Noreen Sher; Abid, Syed Ali; Tripathi, Dharmendra; Mir, Nazir Ahmed

    2017-03-01

    The transport of single-wall carbon nanotube (CNT) nanofluids with temperature-dependent variable viscosity is analyzed by peristaltically driven flow. The main flow problem has been modeled using cylindrical coordinates and flow equations are simplified to ordinary differential equations using long wavelength and low Reynolds' number approximation. Analytical solutions have been obtained for axial velocity, pressure gradient and temperature. Results acquired are discussed graphically for better understanding. It is observed that with an increment in the Grashof number the velocity of the governing fluids starts to decrease significantly and the pressure gradient is higher for pure water as compared to single-walled carbon nanotubes due to low density. As the specific heat is very high for pure water as compared to the multi-wall carbon nanotubes, it raises temperature of the muscles, in the case of pure water, as compared to the multi-walled carbon nanotubes. Furthermore, it is noticed that the trapped bolus starts decreasing in size as the buoyancy forces are dominant as compared to viscous forces. This model may be applicable in biomedical engineering and nanotechnology to design the biomedical devices.

  16. Olfactory map formation in the Drosophila brain: genetic specificity and neuronal variability.

    Science.gov (United States)

    Brochtrup, Anna; Hummel, Thomas

    2011-02-01

    The development of the Drosophila olfactory system is a striking example of how genetic programs specify a large number of different neuron types and assemble them into functional circuits. To ensure precise odorant perception, each sensory neuron has to not only select a single olfactory receptor (OR) type out of a large genomic repertoire but also segregate its synaptic connections in the brain according to the OR class identity. Specification and patterning of second-order interneurons in the olfactory brain center occur largely independent of sensory input, followed by a precise point-to-point matching of sensory and relay neurons. Here we describe recent progress in the understanding of how cell-intrinsic differentiation programs and context-dependent cellular interactions generate a stereotyped sensory map in the Drosophila brain. Recent findings revealed an astonishing morphological diversity among members of the same interneuron class, suggesting an unexpected variability in local microcircuits involved in insect sensory processing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Construction of adjoint operators for coupled equations depending on different variables

    International Nuclear Information System (INIS)

    Hoogenboom, J.E.

    1986-01-01

    A procedure is described for the construction of the adjoint operator matrix in case of coupled equations defining quantities that depend on different sets of variables. This case is not properly treated in the literature. From this procedure a simple rule can be deduced for the construction of such adjoint operator matrices

  18. Human Performance Technology (HPT): An Examination of Definitions through Dependent and Independent Variables.

    Science.gov (United States)

    Irlbeck, Sonja A.

    2002-01-01

    Provides a chronological perspective of human performance technology (HPT) definitions and an evaluation of them in terms of independent and dependent variables. Discusses human competence and performance technology and compares the definitions with the goals that have been articulated for HPT. (Author/LRW)

  19. Central limit theorem for the Banach-valued weakly dependent random variables

    International Nuclear Information System (INIS)

    Dmitrovskij, V.A.; Ermakov, S.V.; Ostrovskij, E.I.

    1983-01-01

    The central limit theorem (CLT) for the Banach-valued weakly dependent random variables is proved. In proving CLT convergence of finite-measured (i.e. cylindrical) distributions is established. A weak compactness of the family of measures generated by a certain sequence is confirmed. The continuity of the limiting field is checked

  20. Short-term memory for event duration: modality specificity and goal dependency.

    Science.gov (United States)

    Takahashi, Kohske; Watanabe, Katsumi

    2012-11-01

    Time perception is involved in various cognitive functions. This study investigated the characteristics of short-term memory for event duration by examining how the length of the retention period affects inter- and intramodal duration judgment. On each trial, a sample stimulus was followed by a comparison stimulus, after a variable delay period (0.5-5 s). The sample and comparison stimuli were presented in the visual or auditory modality. The participants determined whether the comparison stimulus was longer or shorter than the sample stimulus. The distortion pattern of subjective duration during the delay period depended on the sensory modality of the comparison stimulus but was not affected by that of the sample stimulus. When the comparison stimulus was visually presented, the retained duration of the sample stimulus was shortened as the delay period increased. Contrarily, when the comparison stimulus was presented in the auditory modality, the delay period had little to no effect on the retained duration. Furthermore, whenever the participants did not know the sensory modality of the comparison stimulus beforehand, the effect of the delay period disappeared. These results suggest that the memory process for event duration is specific to sensory modality and that its performance is determined depending on the sensory modality in which the retained duration will be used subsequently.

  1. Integration of aerial imaging and variable-rate technology for site-specific aerial herbicide application

    Science.gov (United States)

    As remote sensing and variable rate technology are becoming more available for aerial applicators, practical methodologies on effective integration of these technologies are needed for site-specific aerial applications of crop production and protection materials. The objectives of this study were to...

  2. Method of nuclear reactor control using a variable temperature load dependent set point

    International Nuclear Information System (INIS)

    Kelly, J.J.; Rambo, G.E.

    1982-01-01

    A method and apparatus for controlling a nuclear reactor in response to a variable average reactor coolant temperature set point is disclosed. The set point is dependent upon percent of full power load demand. A manually-actuated ''droop mode'' of control is provided whereby the reactor coolant temperature is allowed to drop below the set point temperature a predetermined amount wherein the control is switched from reactor control rods exclusively to feedwater flow

  3. TWO MEASURES OF THE DEPENDENCE OF PREFERENTIAL RANKINGS ON CATEGORICAL VARIABLES

    Directory of Open Access Journals (Sweden)

    Lissowski Grzegorz

    2017-06-01

    Full Text Available The aim of this paper is to apply a general methodology for constructing statistical methods, which is based on decision theory, to give a statistical description of preferential rankings, with a focus on the rankings’ dependence on categorical variables. In the paper, I use functions of description errors that are based on the Kemeny and Hamming distances between preferential orderings, but the proposed methodology can also be applied to other methods of estimating description errors.

  4. An edgeworth expansion for a sum of M-Dependent random variables

    Directory of Open Access Journals (Sweden)

    Wan Soo Rhee

    1985-01-01

    Full Text Available Given a sequence X1,X2,…,Xn of m-dependent random variables with moments of order 3+α (0<α≦1, we give an Edgeworth expansion of the distribution of Sσ−1(S=X1+X2+…+Xn, σ2=ES2 under the assumption that E[exp(it Sσ1] is small away from the origin. The result is of the best possible order.

  5. BAYESIAN TECHNIQUES FOR COMPARING TIME-DEPENDENT GRMHD SIMULATIONS TO VARIABLE EVENT HORIZON TELESCOPE OBSERVATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Junhan; Marrone, Daniel P.; Chan, Chi-Kwan; Medeiros, Lia; Özel, Feryal; Psaltis, Dimitrios, E-mail: junhankim@email.arizona.edu [Department of Astronomy and Steward Observatory, University of Arizona, 933 N. Cherry Avenue, Tucson, AZ 85721 (United States)

    2016-12-01

    The Event Horizon Telescope (EHT) is a millimeter-wavelength, very-long-baseline interferometry (VLBI) experiment that is capable of observing black holes with horizon-scale resolution. Early observations have revealed variable horizon-scale emission in the Galactic Center black hole, Sagittarius A* (Sgr A*). Comparing such observations to time-dependent general relativistic magnetohydrodynamic (GRMHD) simulations requires statistical tools that explicitly consider the variability in both the data and the models. We develop here a Bayesian method to compare time-resolved simulation images to variable VLBI data, in order to infer model parameters and perform model comparisons. We use mock EHT data based on GRMHD simulations to explore the robustness of this Bayesian method and contrast it to approaches that do not consider the effects of variability. We find that time-independent models lead to offset values of the inferred parameters with artificially reduced uncertainties. Moreover, neglecting the variability in the data and the models often leads to erroneous model selections. We finally apply our method to the early EHT data on Sgr A*.

  6. Effects of Variable Production Rate and Time-Dependent Holding Cost for Complementary Products in Supply Chain Model

    Directory of Open Access Journals (Sweden)

    Mitali Sarkar

    2017-01-01

    Full Text Available Recently, a major trend is going to redesign a production system by controlling or making variable the production rate within some fixed interval to maintain the optimal level. This strategy is more effective when the holding cost is time-dependent as it is interrelated with holding duration of products and rate of production. An effort is made to make a supply chain model (SCM to show the joint effect of variable production rate and time-varying holding cost for specific type of complementary products, where those products are made by two different manufacturers and a common retailer makes them bundle and sells bundles to end customers. Demand of each product is specified by stochastic reservation prices with a known potential market size. Those players of the SCM are considered with unequal power. Stackelberg game approach is employed to obtain global optimum solution of the model. An illustrative numerical example, graphical representation, and managerial insights are given to illustrate the model. Results prove that variable production rate and time-dependent holding cost save more than existing literature.

  7. Conductance of partially disordered graphene: crossover from temperature-dependent to field-dependent variable-range hopping

    International Nuclear Information System (INIS)

    Cheah, C Y; Jaurigue, L C; Kaiser, A B; Gómez-Navarro, C

    2013-01-01

    We report an analysis of low-temperature measurements of the conductance of partially disordered reduced graphene oxide, finding that the data follow a simple crossover scenario. At room temperature, the conductance is dominated by two-dimensional (2D) electric field-assisted, thermally driven (Pollak–Riess) variable-range hopping (VRH) through highly disordered regions. However, at lower temperatures T, we find a smooth crossover to follow the exp(−E 0 /E) 1/3 field-driven (Shklovskii) 2D VRH conductance behaviour when the electric field E exceeds a specific crossover value E C (T) 2D =(E a E 0 1/3 /3) 3/4 determined by the scale factors E 0 and E a for the high-field and intermediate-field regimes respectively. Our crossover scenario also accounts well for experimental data reported by other authors for three-dimensional disordered carbon networks, suggesting wide applicability. (paper)

  8. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna

    2011-06-28

    The antigen-binding site of immunoglobulins is formed by six regions, three from the light and three from the heavy chain variable domains, which, on association of the two chains, form the conventional antigen-binding site of the antibody. The mode of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface between the heavy and light chain variable domains and show that there are essentially two different modes for their interaction that can be identified by the presence of key amino acids in specific positions of the antibody sequences. We also show that the different packing modes are related to the type of recognized antigen.

  9. Distance and Azimuthal Dependence of Ground‐Motion Variability for Unilateral Strike‐Slip Ruptures

    KAUST Repository

    Vyas, Jagdish Chandra

    2016-06-21

    We investigate near‐field ground‐motion variability by computing the seismic wavefield for five kinematic unilateral‐rupture models of the 1992 Mw 7.3 Landers earthquake, eight simplified unilateral‐rupture models based on the Landers event, and a large Mw 7.8 ShakeOut scenario. We include the geometrical fault complexity and consider different 1D velocity–density profiles for the Landers simulations and a 3D heterogeneous Earth structure for the ShakeOut scenario. For the Landers earthquake, the computed waveforms are validated using strong‐motion recordings. We analyze the simulated ground‐motion data set in terms of distance and azimuth dependence of peak ground velocity (PGV). Our simulations reveal that intraevent ground‐motion variability Graphic is higher in close distances to the fault (<20  km) and decreases with increasing distance following a power law. This finding is in stark contrast to constant sigma‐values used in empirical ground‐motion prediction equations. The physical explanation of a large near‐field Graphic is the presence of strong directivity and rupture complexity. High values of Graphic occur in the rupture‐propagation direction, but small values occur in the direction perpendicular to it. We observe that the power‐law decay of Graphic is primarily controlled by slip heterogeneity. In addition, Graphic, as function of azimuth, is sensitive to variations in both rupture speed and slip heterogeneity. The azimuth dependence of the ground‐motion mean μln(PGV) is well described by a Cauchy–Lorentz function that provides a novel empirical quantification to model the spatial dependency of ground motion. Online Material: Figures of slip distributions, residuals to ground‐motion prediction equations (GMPEs), distance and azimuthal dependence, and directivity predictor of ground‐motion variability for different source models.

  10. Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent.

    Science.gov (United States)

    Winham, Stacey J; Preuss, Ulrich W; Geske, Jennifer R; Zill, Peter; Heit, John A; Bakalkin, Georgy; Biernacka, Joanna M; Karpyak, Victor M

    2015-10-27

    We previously demonstrated that prodynorphin (PDYN) haplotypes and single nucleotide polymorphism (SNP) rs2281285 are associated with alcohol dependence and the propensity to drink in negative emotional states, and recent studies suggest that PDYN gene effects on substance dependence risk may be sex-related. We examined sex-dependent associations of PDYN variation with alcohol dependence and related phenotypes, including negative craving, time until relapse after treatment and the length of sobriety episodes before seeking treatment, in discovery and validation cohorts of European ancestry. We found a significant haplotype-by-sex interaction (p  =  0.03), suggesting association with alcohol dependence in males (p = 1E-4) but not females. The rs2281285 G allele increased risk for alcohol dependence in males in the discovery cohort (OR = 1.49, p = 0.002), with a similar trend in the validation cohort (OR = 1.35, p = 0.086). However, rs2281285 showed a trend towards association with increased negative craving in females in both the discovery (beta = 10.16, p = 0.045) and validation samples (OR = 7.11, p = 0.066). In the discovery cohort, rs2281285 was associated with time until relapse after treatment in females (HR = 1.72, p = 0.037); in the validation cohort, it was associated with increased length of sobriety episodes before treatment in males (beta = 13.49, p = 0.001). Our findings suggest that sex-dependent effects of PDYN variants in alcohol dependence are phenotype-specific.

  11. Degree of multicollinearity and variables involved in linear dependence in additive-dominant models

    Directory of Open Access Journals (Sweden)

    Juliana Petrini

    2012-12-01

    Full Text Available The objective of this work was to assess the degree of multicollinearity and to identify the variables involved in linear dependence relations in additive-dominant models. Data of birth weight (n=141,567, yearling weight (n=58,124, and scrotal circumference (n=20,371 of Montana Tropical composite cattle were used. Diagnosis of multicollinearity was based on the variance inflation factor (VIF and on the evaluation of the condition indexes and eigenvalues from the correlation matrix among explanatory variables. The first model studied (RM included the fixed effect of dam age class at calving and the covariates associated to the direct and maternal additive and non-additive effects. The second model (R included all the effects of the RM model except the maternal additive effects. Multicollinearity was detected in both models for all traits considered, with VIF values of 1.03 - 70.20 for RM and 1.03 - 60.70 for R. Collinearity increased with the increase of variables in the model and the decrease in the number of observations, and it was classified as weak, with condition index values between 10.00 and 26.77. In general, the variables associated with additive and non-additive effects were involved in multicollinearity, partially due to the natural connection between these covariables as fractions of the biological types in breed composition.

  12. The dependence of J/ψ-nucleon inelastic cross section on the Feynman variable

    International Nuclear Information System (INIS)

    Duan Chungui; Liu Na; Miao Wendan

    2011-01-01

    By means of two typical sets of nuclear parton distribution functions, meanwhile taking account of the energy loss of the beam proton and the nuclear absorption of the charmonium states traversing the nuclear matter in the uniform framework of the Glauber model, a leading order phenomenological analysis is given in the color evaporation model of the E866 experimental data on J/ψ production differential cross section ratios R Fe/Be (x F ). It is shown that the energy loss effect of beam proton on R Fe/Be (x F ) is more important than the nuclear effects on parton distribution functions in the high Feynman variable x F region. It is found that the J/ψ-nucleon inelastic cross section depends on the Feynman variable x F and increases linearly with x F in the region x F > 0.2. (authors)

  13. Bioaccumulation of photoprotective compounds in copepods: environmental triggers and sources of intra-specific variability

    Science.gov (United States)

    Zagarese, H. E.; García, P.; Diéguez, M. D.; Ferraro, M. A.

    2012-12-01

    Ultraviolet radiation (UVR) and temperature are two globally important abiotic factors affecting freshwater ecosystems. Planktonic organisms have developed a battery of counteracting mechanisms to minimize the risk of being damaged by UVR, which respond to three basic principles: avoid, protect, repair. Copepods are among the most successful zooplankton groups. They are highly adaptable animals, capable of displaying flexible behaviors, physiologies, and life strategies. In particular, they are well equipped to cope with harmful UVR. Their arsenal includes vertical migration, accumulation of photoprotective compounds, and photorepair. The preference for a particular strategy is affected by a plethora of environmental (extrinsic) parameters, such as the existence of a depth refuge, the risk of visual predation, and temperature. Temperature modifies the environment (e.g. the lake thermal structure), and animal metabolism (e.g., swimming speed, bioaccumulation of photoprotective compounds). In addition, the relative weight of UVR-coping strategies is also influenced by the organism (intrinsic) characteristics (e.g., inter- and intra-specific variability). The UV absorbing compounds, mycosporine-like amino acids (MAAs), are widely distributed among freshwater copepods. Animals are unable to synthesize MAAs, and therefore depend on external sources for accumulating these compounds. Although copepods may acquire MAAs from their food, for the few centropagic species investigated so far, the main source of MAAs are microbial (most likely prokaryotic) organisms living in close association with the copepods. Boeckella gracilipes is a common centropagic copepod in Patagonian lakes. We suspected that its occurrence in different types of lakes, hydrologically unconnected, but within close geographical proximity, could have resulted in different microbial-copepod associations (i.e., different MAAs sources) that could translate into intra-specific differences in the accumulation

  14. Building the nodal nuclear data dependences in a many-dimensional state-variable space

    International Nuclear Information System (INIS)

    Dufek, Jan

    2011-01-01

    Highlights: → The Abstract and Introduction are revised to reflect reviewers' comments. → Section is revised and simplified. → The third paragraph in Section is revised. → All typos are fixed. - Abstract: We present new methods for building the polynomial-regression based nodal nuclear data models. The data models can reflect dependences on a large number of state variables, and they can consider various history effects. Suitable multivariate polynomials that approximate the nodal data dependences are identified efficiently in an iterative manner. The history effects are analysed using a new sampling scheme for lattice calculations where the traditional base burnup and branch calculations are replaced by a large number of diverse burnup histories. The total number of lattice calculations is controlled so that the data models are built to a required accuracy.

  15. Memory effects, two color percolation, and the temperature dependence of Mott variable-range hopping

    Science.gov (United States)

    Agam, Oded; Aleiner, Igor L.

    2014-06-01

    There are three basic processes that determine hopping transport: (a) hopping between normally empty sites (i.e., having exponentially small occupation numbers at equilibrium), (b) hopping between normally occupied sites, and (c) transitions between normally occupied and unoccupied sites. In conventional theories all these processes are considered Markovian and the correlations of occupation numbers of different sites are believed to be small (i.e., not exponential in temperature). We show that, contrary to this belief, memory effects suppress the processes of type (c) and manifest themselves in a subleading exponential temperature dependence of the variable-range hopping conductivity. This temperature dependence originates from the property that sites of type (a) and (b) form two independent resistor networks that are weakly coupled to each other by processes of type (c). This leads to a two-color percolation problem which we solve in the critical region.

  16. Specific immunotherapy modifies allergen-specific CD4+ T cell responses in an epitope-dependent manner

    Science.gov (United States)

    Wambre, Erik; DeLong, Jonathan H.; James, Eddie A.; Torres-Chinn, Nadia; Pfützner, Wolfgang; Möbs, Christian; Durham, Stephen R.; Till, Stephen J.; Robinson, David; Kwok, William W.

    2014-01-01

    Background Understanding the mechanisms by which the immune system induces and controls allergic inflammation at the T cell epitope level is critical for the design of new allergy vaccine strategies. Objective To characterize allergen-specific T cell responses linked with allergy or peripheral tolerance and to determine how CD4+ T cell responses to individual allergen-derived epitopes change over allergen-specific immunotherapy (ASIT). Methods Timothy grass pollen (TGP) allergy was used as a model for studying grass pollen allergies. The breadth, magnitude, epitope hierarchy and phenotype of the DR04:01-restricted TGP-specific T cell responses in ten grass pollen allergic, five non-atopic and six allergy vaccine-treated individuals was determined using an ex vivo pMHCII-tetramer approach. Results CD4+ T cells in allergic individuals are directed to a broad range of TGP epitopes characterized by defined immunodominance hierarchy patterns and with distinct functional profiles that depend on the epitope recognized. Epitopes that are restricted specifically to either TH2 or TH1/TR1 responses were identified. ASIT was associated with preferential deletion of allergen-specific TH2 cells and without significant change in frequency of TH1/TR1 cells. Conclusions Preferential allergen-specific TH2-cells deletion after repeated high doses antigen stimulation can be another independent mechanism to restore tolerance to allergen during immunotherapy. PMID:24373351

  17. Population and prehistory III: food-dependent demography in variable environments.

    Science.gov (United States)

    Lee, Charlotte T; Puleston, Cedric O; Tuljapurkar, Shripad

    2009-11-01

    The population dynamics of preindustrial societies depend intimately on their surroundings, and food is a primary means through which environment influences population size and individual well-being. Food production requires labor; thus, dependence of survival and fertility on food involves dependence of a population's future on its current state. We use a perturbation approach to analyze the effects of random environmental variation on this nonlinear, age-structured system. We show that in expanding populations, direct environmental effects dominate induced population fluctuations, so environmental variability has little effect on mean hunger levels, although it does decrease population growth. The growth rate determines the time until population is limited by space. This limitation introduces a tradeoff between population density and well-being, so population effects become more important than the direct effects of the environment: environmental fluctuation increases mortality, releasing density dependence and raising average well-being for survivors. We discuss the social implications of these findings for the long-term fate of populations as they transition from expansion into limitation, given that conditions leading to high well-being during growth depress well-being during limitation.

  18. Numerical Solution of the Time-Dependent Navier–Stokes Equation for Variable Density–Variable Viscosity. Part I

    Czech Academy of Sciences Publication Activity Database

    Axelsson, Owe; Xin, H.; Neytcheva, M.

    2015-01-01

    Roč. 20, č. 2 (2015), s. 232-260 ISSN 1392-6292 Institutional support: RVO:68145535 Keywords : variable density * phase-field model * Navier-Stokes equations * preconditioning * variable viscosity Subject RIV: BA - General Mathematics Impact factor: 0.468, year: 2015 http://www.tandfonline.com/doi/abs/10.3846/13926292.2015.1021395

  19. Phage exposure causes dynamic shifts in the expression states of specific phase-variable genes of Campylobacter jejuni

    DEFF Research Database (Denmark)

    Aidley, Jack; Holst Sørensen, Martine C.; Bayliss, Christopher D.

    2017-01-01

    Phase variation (PV) creates phenotypic heterogeneity at high frequencies and in a reversible manner. This phenomenon allows bacteria to adapt to a variety of different environments and selective pressures. In Campylobacter jejuni this reversible adaptive process is mediated by mutations in homop......Phase variation (PV) creates phenotypic heterogeneity at high frequencies and in a reversible manner. This phenomenon allows bacteria to adapt to a variety of different environments and selective pressures. In Campylobacter jejuni this reversible adaptive process is mediated by mutations...... in homopolymeric G/C tracts. Many C. jejuni-specific phages are dependent on phase-variable surface structures for successful infection. We previously identified the capsular polysaccharide (CPS) moiety, MeOPN-GalfNAc, as a receptor for phage F336 and showed that phase-variable expression of the transferase...... for this CPS modification, cj1421, and two other phase-variable CPS genes generated phage resistance in C. jejuni. Here we investigate the population dynamics of C. jejuni NCTC11168 when exposed to phage F336 in vitro using a newly described method - the 28-locus-CJ11168 PV analysis. Dynamic switching...

  20. Sensitivity, Specificity and Predictive Value of Heart Rate Variability Indices in Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Anne Kastelianne França da Silva

    Full Text Available Abstract Background: Heart rate variability (HRV indices may detect autonomic changes with good diagnostic accuracy. Type diabetes mellitus (DM individuals may have changes in autonomic modulation; however, studies of this nature in this population are still scarce. Objective: To compare HRV indices between and assess their prognostic value by measurements of sensitivity, specificity and predictive values in young individuals with type 1 DM and healthy volunteers. Methods: In this cross-sectional study, physical and clinical assessment was performed in 39 young patients with type 1 DM and 43 young healthy controls. For HRV analysis, beat-to-beat heart rate variability was measured in dorsal decubitus, using a Polar S810i heart rate monitor, for 30 minutes. The following indices were calculated: SDNN, RMSSD, PNN50, TINN, RRTri, LF ms2, HF ms2, LF un, HF un, LF/HF, SD1, SD2, SD1/SD2, and ApEn. Results: Type 1 DM subjects showed a decrease in sympathetic and parasympathetic activities, and overall variability of autonomic nervous system. The RMSSD, SDNN, PNN50, LF ms2, HF ms2, RRTri, SD1 and SD2 indices showed greater diagnostic accuracy in discriminating diabetic from healthy individuals. Conclusion: Type 1 DM individuals have changes in autonomic modulation. The SDNN, RMSSD, PNN50, RRtri, LF ms2, HF ms2, SD1 and SD2 indices may be alternative tools to discriminate individuals with type 1 DM.

  1. Uncovering state-dependent relationships in shallow lakes using Bayesian latent variable regression.

    Science.gov (United States)

    Vitense, Kelsey; Hanson, Mark A; Herwig, Brian R; Zimmer, Kyle D; Fieberg, John

    2018-03-01

    Ecosystems sometimes undergo dramatic shifts between contrasting regimes. Shallow lakes, for instance, can transition between two alternative stable states: a clear state dominated by submerged aquatic vegetation and a turbid state dominated by phytoplankton. Theoretical models suggest that critical nutrient thresholds differentiate three lake types: highly resilient clear lakes, lakes that may switch between clear and turbid states following perturbations, and highly resilient turbid lakes. For effective and efficient management of shallow lakes and other systems, managers need tools to identify critical thresholds and state-dependent relationships between driving variables and key system features. Using shallow lakes as a model system for which alternative stable states have been demonstrated, we developed an integrated framework using Bayesian latent variable regression (BLR) to classify lake states, identify critical total phosphorus (TP) thresholds, and estimate steady state relationships between TP and chlorophyll a (chl a) using cross-sectional data. We evaluated the method using data simulated from a stochastic differential equation model and compared its performance to k-means clustering with regression (KMR). We also applied the framework to data comprising 130 shallow lakes. For simulated data sets, BLR had high state classification rates (median/mean accuracy >97%) and accurately estimated TP thresholds and state-dependent TP-chl a relationships. Classification and estimation improved with increasing sample size and decreasing noise levels. Compared to KMR, BLR had higher classification rates and better approximated the TP-chl a steady state relationships and TP thresholds. We fit the BLR model to three different years of empirical shallow lake data, and managers can use the estimated bifurcation diagrams to prioritize lakes for management according to their proximity to thresholds and chance of successful rehabilitation. Our model improves upon

  2. Parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner.

    Science.gov (United States)

    Otani, Koichi; Suzuki, Akihito; Matsumoto, Yoshihiko; Shibuya, Naoshi; Sadahiro, Ryoichi; Enokido, Masanori

    2013-12-24

    It has been suggested that dysfunctional attitudes, cognitive vulnerability to depression, have developmental origins. The present study examined the effects of parental rearing on dysfunctional attitudes in three areas of life with special attention to gender specificity. The subjects were 665 Japanese healthy volunteers. Dysfunctional attitudes were assessed by the 24-item Dysfunctional Attitude Scale, which has the Achievement, Dependency and Self-control subscales. Perceived parental rearing was assessed by the Parental Bonding Instrument, which has the Care and Protection subscales. Higher scores of the Achievement (β = 0.293, p overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner.

  3. Leaf area index from litter collection: impact of specific leaf area variability within a beech stand

    Energy Technology Data Exchange (ETDEWEB)

    Bouriaud, O. [Inst. National de la Recherche Agronomique, Centre de Recherches Forestieres de Nancy, Champenoux (France); Soudani, K. [Univ. Paris-Sud XI, Dept. d' Ecophysiologie Vegetale, Lab. Ecologie Systematique et Evolution, Orsay Cedex (France); Breda, N. [Inst. National de la Recherche Agronomique, Centre de Recherches Forestieres de Nancy, Champenoux (France)

    2003-06-01

    Litter fall collection is a direct method widely used to estimate leaf area index (LAI) in broad-leaved forest stands. Indirect measurements using radiation transmittance and gap fraction theory are often compared and calibrated against litter fall, which is considered as a reference method, but few studies address the question of litter specific leaf area (SLA) measurement and variability. SLA (leaf area per unit of dry weight, m{sup 2}{center_dot}g{sup -1}) is used to convert dry leaf litter biomass (g .m{sup -}2) into leaf area per ground unit area (m{sup 2}{center_dot}m{sup -2}). We paid special attention to this parameter in two young beech stands (dense and thinned) in northeastern France. The variability of both canopy (closure, LAI) and site conditions (soil properties, vegetation) was investigated as potential contributing factors to beech SLA variability. A systematic description of soil and floristic composition was performed and three types of soil were identified. Ellenberg's indicator values were averaged for each plot to assess nitrogen soil content. SLA of beech litter was measured three times during the fall in 23 plots in the stands (40 ha). Litter was collected bimonthly in square-shaped traps (0.5 m{sup 2}) and dried. Before drying, 30 leaves per plot and for each date were sampled, and leaf length, width, and area were measured with the help of a LI-COR areameter. SLA was calculated as the ratio of cumulated leaf area to total dry weight of the 30 leaves. Leaves characteristics per plot were averaged for the three dates of litter collection. Plant area index (PAI), estimated using the LAI-2000 plant canopy analyser and considering only the upper three rings, ranged from 2.9 to 8.1. Specific leaf area of beech litter was also highly different from one plot to the other, ranging from 150 to 320 cm{sup 2}{center_dot}g{sup -1}. Nevertheless, no relationship was found between SLA and stand canopy closure or PAI On the contrary, a significant

  4. Leaf area index from litter collection: impact of specific leaf area variability within a beech stand

    International Nuclear Information System (INIS)

    Bouriaud, O.; Soudani, K.; Breda, N.

    2003-01-01

    Litter fall collection is a direct method widely used to estimate leaf area index (LAI) in broad-leaved forest stands. Indirect measurements using radiation transmittance and gap fraction theory are often compared and calibrated against litter fall, which is considered as a reference method, but few studies address the question of litter specific leaf area (SLA) measurement and variability. SLA (leaf area per unit of dry weight, m 2 ·g -1 ) is used to convert dry leaf litter biomass (g .m - 2) into leaf area per ground unit area (m 2 ·m -2 ). We paid special attention to this parameter in two young beech stands (dense and thinned) in northeastern France. The variability of both canopy (closure, LAI) and site conditions (soil properties, vegetation) was investigated as potential contributing factors to beech SLA variability. A systematic description of soil and floristic composition was performed and three types of soil were identified. Ellenberg's indicator values were averaged for each plot to assess nitrogen soil content. SLA of beech litter was measured three times during the fall in 23 plots in the stands (40 ha). Litter was collected bimonthly in square-shaped traps (0.5 m 2 ) and dried. Before drying, 30 leaves per plot and for each date were sampled, and leaf length, width, and area were measured with the help of a LI-COR areameter. SLA was calculated as the ratio of cumulated leaf area to total dry weight of the 30 leaves. Leaves characteristics per plot were averaged for the three dates of litter collection. Plant area index (PAI), estimated using the LAI-2000 plant canopy analyser and considering only the upper three rings, ranged from 2.9 to 8.1. Specific leaf area of beech litter was also highly different from one plot to the other, ranging from 150 to 320 cm 2 ·g -1 . Nevertheless, no relationship was found between SLA and stand canopy closure or PAI On the contrary, a significant relationship between SLA and soil properties was observed. Both SLA

  5. Natural convection heat transfer of fluid with temperature-dependent specific heat

    International Nuclear Information System (INIS)

    Tanaka, Amane; Kubo, Shinji; Akino, Norio

    1998-01-01

    The present study investigates natural convection from a heated vertical plate of fluid with temperature-dependent specific heat, which is introduced as a model of microencapsulated phase change material slurries (MCPCM slurries). The temperature dependence of specific heat is represented by Gauss function with three physical parameters (peak temperature, width of phase change temperature and latent heat). Boundary layer equations are solved numerically, and the velocity and temperature fields of the flow are obtained. The relation between the heat transfer coefficients and the physical parameters of specific heat is discussed. The results show that the velocities and temperatures are smaller, and the heat transfer coefficients are larger comparing with those of the fluid with constant specific heat. (author)

  6. Countermovement jump height: gender and sport-specific differences in the force-time variables.

    Science.gov (United States)

    Laffaye, Guillaume; Wagner, Phillip P; Tombleson, Tom I L

    2014-04-01

    The goal of this study was to assess (a) the eccentric rate of force development, the concentric force, and selected time variables on vertical performance during countermovement jump, (b) the existence of gender differences in these variables, and (c) the sport-specific differences. The sample was composed of 189 males and 84 females, all elite athletes involved in college and professional sports (primarily football, basketball, baseball, and volleyball). The subjects performed a series of 6 countermovement jumps on a force plate (500 Hz). Average eccentric rate of force development (ECC-RFD), total time (TIME), eccentric time (ECC-T), Ratio between eccentric and total time (ECC-T:T) and average force (CON-F) were extracted from force-time curves and the vertical jumping performance, measured by impulse momentum. Results show that CON-F (r = 0.57; p differ between both sexes (p differ, showing a similar temporal structure. The best way to jump high is to increase CON-F and ECC-RFD thus minimizing the ECC-T. Principal component analysis (PCA) accounted for 76.8% of the JH variance and revealed that JH is predicted by a temporal and a force component. Furthermore, the PCA comparison made among athletes revealed sport-specific signatures: volleyball players revealed a temporal-prevailing profile, a weak-force with large ECC-T:T for basketball players and explosive and powerful profiles for football and baseball players.

  7. E-cigarette- specific symptoms of nicotine dependence among Texas adolescents.

    Science.gov (United States)

    Case, Kathleen R; Mantey, Dale S; Creamer, MeLisa R; Harrell, Melissa B; Kelder, Steven H; Perry, Cheryl L

    2018-09-01

    The potential of e-cigarettes to elicit symptoms of nicotine dependence has not been adequately studied, particularly in adolescent populations. The present study examined the prevalence of e-cigarette-specific symptoms of nicotine dependence ("symptoms of e-cigarette dependence") and the associations between these symptoms, e-cigarette usage group, and e-cigarette cessation-related items among Texas adolescents. This study involved a cross-sectional analysis of adolescents from Wave 4 of the Texas Adolescent Tobacco and Marketing Surveillance System (TATAMS) (n = 2891/N = 461,069). Chi-Square analyses examined differences in the prevalence of symptoms of dependence by e-cigarette usage group (exclusive versus dual users of e-cigarettes and combustible tobacco products) and demographic characteristics. Weighted multivariable logistic regression analyses examined the associations between symptoms of e-cigarette dependence, e-cigarette usage group, and e-cigarette cessation items. Exclusive e-cigarette users experienced symptoms of e-cigarette dependence, although the prevalence of most of the symptoms was higher for dual users. Adolescents who reported more symptoms of dependence were less likely to report both wanting to quit e-cigarettes and a past-year quit attempt for e-cigarettes (adjusted odds ratio "AOR" = 0.61 (95% CI = 0.41, 0.92) and AOR = 0.52 (95% CI = 0.30, 0.92), respectively). This study is the first to demonstrate that adolescent e-cigarette users are experiencing symptoms of dependence specific to e-cigarettes. In addition, symptoms of dependence may be barriers to e-cigarette cessation. Future research is needed to determine if characteristics of e-cigarette use (e.g. frequency and intensity) are associated with dependence. Copyright © 2018. Published by Elsevier Ltd.

  8. [Correlation coefficient-based classification method of hydrological dependence variability: With auto-regression model as example].

    Science.gov (United States)

    Zhao, Yu Xi; Xie, Ping; Sang, Yan Fang; Wu, Zi Yi

    2018-04-01

    Hydrological process evaluation is temporal dependent. Hydrological time series including dependence components do not meet the data consistency assumption for hydrological computation. Both of those factors cause great difficulty for water researches. Given the existence of hydrological dependence variability, we proposed a correlationcoefficient-based method for significance evaluation of hydrological dependence based on auto-regression model. By calculating the correlation coefficient between the original series and its dependence component and selecting reasonable thresholds of correlation coefficient, this method divided significance degree of dependence into no variability, weak variability, mid variability, strong variability, and drastic variability. By deducing the relationship between correlation coefficient and auto-correlation coefficient in each order of series, we found that the correlation coefficient was mainly determined by the magnitude of auto-correlation coefficient from the 1 order to p order, which clarified the theoretical basis of this method. With the first-order and second-order auto-regression models as examples, the reasonability of the deduced formula was verified through Monte-Carlo experiments to classify the relationship between correlation coefficient and auto-correlation coefficient. This method was used to analyze three observed hydrological time series. The results indicated the coexistence of stochastic and dependence characteristics in hydrological process.

  9. Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

    Science.gov (United States)

    Ahn, Woo-Young; Vassileva, Jasmin

    2016-04-01

    Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Variability of Surface Reflection Amplitudes of GPR Horn Antenna Depending on Distance between Antenna and Surface

    Directory of Open Access Journals (Sweden)

    Komačka Jozef

    2016-05-01

    Full Text Available The study focused on variability of surface reflections amplitudes of GPR horn antenna in relation to distance between an antenna and a surface is presented in the paper. The air-coupled antenna with the central frequency of 1 GHz was used in the investigation. Four types of surfaces (dry pavement, wet pavement, metal plate and composite layer from gypsum and wood were tested. The distance of antenna above the surfaces was changed in the range from 37.5 cm to 53.5 cm. The amplitudes of negative and positive peaks and their variability were analysed in relation to the distance of antenna above the surfaces. Moreover, the influence of changes in the peaks of negative and positive amplitudes on the total amplitudes was assessed. It was found out the amplitudes of negative peaks for all investigated surfaces were relatively consistent in the range from 40.5 cm to 48.5 cm and the moderate decline was identified in the case of amplitudes of positive peaks in the range of distances from 37.5 cm to 51.5 cm. This decline influences the tendency of total amplitudes. Based on the results of analysis it can be stated the distance of air-coupled antenna above the surface can influence the value of total amplitude and the differences depend on the type of surface.

  11. Root biomass production in populations of six rooted macrophytes in response to Cu exposure: intra-specific variability versus constitutive-like tolerance.

    Science.gov (United States)

    Marchand, L; Nsanganwimana, F; Lamy, J B; Quintela-Sabaris, C; Gonnelli, C; Colzi, I; Fletcher, T; Oustrière, N; Kolbas, A; Kidd, P; Bordas, F; Newell, P; Alvarenga, P; Deletic, A; Mench, M

    2014-10-01

    Intra-specific variability of root biomass production (RP) of six rooted macrophytes, i.e. Juncus effusus, Phragmites australis, Schoenoplectus lacustris, Typha latifolia, Phalaris arundinacea, and Iris pseudacorus grown from clones, in response to Cu exposure was investigated. Root biomass production varied widely for all these macrophytes in control conditions (0.08 μM) according to the sampling site. Root biomass production of T. latifolia and I. pseudacorus in the 2.5-25 μM Cu range depended on the sampling location but not on the Cu dose in the growth medium. For P. australis, J. effusus, S. lacustris, and P. arundinacea, an intra-specific variability of RP depending on both the sampling location and the Cu-dose was evidenced. This intra-specific variability of RP depending on the sampling location and of Cu-tolerance for these last four species suggests that Cu constitutive tolerance for all rooted macrophytes is not a species-wide trait but it exhibits variability for some species. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. DREAM Controls the On/Off Switch of Specific Activity-Dependent Transcription Pathways

    Science.gov (United States)

    Mellström, Britt; Sahún, Ignasi; Ruiz-Nuño, Ana; Murtra, Patricia; Gomez-Villafuertes, Rosa; Savignac, Magali; Oliveros, Juan C.; Gonzalez, Paz; Kastanauskaite, Asta; Knafo, Shira; Zhuo, Min; Higuera-Matas, Alejandro; Errington, Michael L.; Maldonado, Rafael; DeFelipe, Javier; Jefferys, John G. R.; Bliss, Tim V. P.; Dierssen, Mara

    2014-01-01

    Changes in nuclear Ca2+ homeostasis activate specific gene expression programs and are central to the acquisition and storage of information in the brain. DREAM (downstream regulatory element antagonist modulator), also known as calsenilin/KChIP-3 (K+ channel interacting protein 3), is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. To study the function of DREAM in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Using genome-wide analysis, we show that DREAM regulates the expression of specific activity-dependent transcription factors in the hippocampus, including Npas4, Nr4a1, Mef2c, JunB, and c-Fos. Furthermore, DREAM regulates its own expression, establishing an autoinhibitory feedback loop to terminate activity-dependent transcription. Ablation of DREAM does not modify activity-dependent transcription because of gene compensation by the other KChIP family members. The expression of daDREAM in the forebrain resulted in a complex phenotype characterized by loss of recurrent inhibition and enhanced long-term potentiation (LTP) in the dentate gyrus and impaired learning and memory. Our results indicate that DREAM is a major master switch transcription factor that regulates the on/off status of specific activity-dependent gene expression programs that control synaptic plasticity, learning, and memory. PMID:24366545

  13. An analysis of boundary-effects in obtaining the frequency dependent specific heat by effusivity measurements

    DEFF Research Database (Denmark)

    Christensen, Tage Emil; Behrens, Claus

    The frequency dependent specific heat is a significant response function characterizing the glass transition. Contrary to the dielectric response it is not easily measured over many decades. The introduction of the 3-omega method, where the temperature oscillations at a planar oscillatoric heat g...

  14. Effects of variable specific heat on energy transfer in a high-temperature supersonic channel flow

    Science.gov (United States)

    Chen, Xiaoping; Li, Xiaopeng; Dou, Hua-Shu; Zhu, Zuchao

    2018-05-01

    An energy transfer mechanism in high-temperature supersonic turbulent flow for variable specific heat (VSH) condition through turbulent kinetic energy (TKE), mean kinetic energy (MKE), turbulent internal energy (TIE) and mean internal energy (MIE) is proposed. The similarities of energy budgets between VSH and constant specific heat (CSH) conditions are investigated by introducing a vibrational energy excited degree and considering the effects of fluctuating specific heat. Direct numerical simulation (DNS) of temporally evolving high-temperature supersonic turbulent channel flow is conducted at Mach number 3.0 and Reynolds number 4800 combined with a constant dimensional wall temperature 1192.60 K for VSH and CSH conditions to validate the proposed energy transfer mechanism. The differences between the terms in the two kinetic energy budgets for VSH and CSH conditions are small; however, the magnitude of molecular diffusion term for VSH condition is significantly smaller than that for CSH condition. The non-negligible energy transfer is obtained after neglecting several small terms of diffusion, dissipation and compressibility related. The non-negligible energy transfer involving TIE includes three processes, in which energy can be gained from TKE and MIE and lost to MIE. The same non-negligible energy transfer through TKE, MKE and MIE is observed for both the conditions.

  15. A Plasma Diagnostic Set for the Study of a Variable Specific Impulse Magnetoplasma Rocket

    Science.gov (United States)

    Squire, J. P.; Chang-Diaz, F. R.; Bengtson Bussell, R., Jr.; Jacobson, V. T.; Wootton, A. J.; Bering, E. A.; Jack, T.; Rabeau, A.

    1997-11-01

    The Advanced Space Propulsion Laboratory (ASPL) is developing a Variable Specific Impulse Magnetoplasma Rocket (VASIMR) using an RF heated magnetic mirror operated asymmetrically. We will describe the initial set of plasma diagnostics and data acquisition system being developed and installed on the VASIMR experiment. A U.T. Austin team is installing two fast reciprocating probes: a quadruple Langmuir and a Mach probe. These measure electron density and temperature profiles, electrostatic plasma fluctuations, and plasma flow profiles. The University of Houston is developing an array of 20 highly directional Retarding Potential Analyzers (RPA) for measuring ion energy distribution function profiles in the rocket plume, giving a measurement of total thrust. We have also developed a CAMAC based data acquisition system using LabView running on a Power Macintosh communicating through a 2 MB/s serial highway. We will present data from initial plasma operations and discuss future diagnostic development.

  16. Specific transfer effects following variable priority dual-task training in older adults.

    Science.gov (United States)

    Lussier, Maxime; Bugaiska, Aurélia; Bherer, Louis

    2017-01-01

    Past divided attention training studies in older adults have suggested that variable priority training (VPT) tends to show larger improvement than fixed priority training (FPT). However, it remains unclear whether VPT leads to larger transfer effects. In this study, eighty-three older adults aged between 55 and 65 received five 1-hour sessions of VPT, FPT or of an active placebo. VPT and FPT subjects trained on a complex dual-task condition with variable stimulus timings in order to promote more flexible and self-guided strategies with regard to attentional priority devoted to the concurrent tasks. Real-time individualized feedback was provided to encourage improvement. The active placebo group attended computer classes. Near and far modality transfer tasks were used to assess the generalization of transfer effects. Results showed that VPT induced significantly larger transfer effects than FPT on a near modality transfer task. Evidence for larger transfer effects in VPT than FPT on a far modality transfer task was also observed. Furthermore, the superiority of VPT on FPT in transfer effects was specific to the ability to coordinate two concurrent tasks. Results of this study help better understand the benefits of VPT attentional training on transfer effects, which is an essential outcome for cognitive training effectiveness and relevancy.

  17. Site-Specific Variability in the Chemical Diversity of the Antarctic Red Alga Plocamium cartilagineum

    Directory of Open Access Journals (Sweden)

    Ryan M. Young

    2013-06-01

    Full Text Available Plocamium cartilagineum is a common red alga on the benthos of Antarctica and can be a dominant understory species along the western Antarctic Peninsula. Algae from this region have been studied chemically, and like “P. cartilagineum” from other worldwide locations where it is common, it is rich in halogenated monoterpenes, some of which have been implicated as feeding deterrents toward sympatric algal predators. Secondary metabolites are highly variable in this alga, both qualitatively and quantitatively, leading us to probe individual plants to track the possible link of variability to genetic or other factors. Using cox1 and rbcL gene sequencing, we find that the Antarctic alga divides into two closely related phylogroups, but not species, each of which is further divided into one of five chemogroups. The chemogroups themselves, defined on the basis of Bray-Curtis similarity profiling of GC/QqQ chromatographic analyses, are largely site specific within a 10 km2 area. Thus, on the limited geographical range of this analysis, P. cartilagineum displays only modest genetic radiation, but its secondary metabolome was found to have experienced more extensive radiation. Such metabogenomic divergence demonstrated on the larger geographical scale of the Antarctic Peninsula, or perhaps even continent-wide, may contribute to the discovery of cryptic speciation.

  18. Evaluating Variability and Uncertainty of Geological Strength Index at a Specific Site

    Science.gov (United States)

    Wang, Yu; Aladejare, Adeyemi Emman

    2016-09-01

    Geological Strength Index (GSI) is an important parameter for estimating rock mass properties. GSI can be estimated from quantitative GSI chart, as an alternative to the direct observational method which requires vast geological experience of rock. GSI chart was developed from past observations and engineering experience, with either empiricism or some theoretical simplifications. The GSI chart thereby contains model uncertainty which arises from its development. The presence of such model uncertainty affects the GSI estimated from GSI chart at a specific site; it is, therefore, imperative to quantify and incorporate the model uncertainty during GSI estimation from the GSI chart. A major challenge for quantifying the GSI chart model uncertainty is a lack of the original datasets that have been used to develop the GSI chart, since the GSI chart was developed from past experience without referring to specific datasets. This paper intends to tackle this problem by developing a Bayesian approach for quantifying the model uncertainty in GSI chart when using it to estimate GSI at a specific site. The model uncertainty in the GSI chart and the inherent spatial variability in GSI are modeled explicitly in the Bayesian approach. The Bayesian approach generates equivalent samples of GSI from the integrated knowledge of GSI chart, prior knowledge and observation data available from site investigation. Equations are derived for the Bayesian approach, and the proposed approach is illustrated using data from a drill and blast tunnel project. The proposed approach effectively tackles the problem of how to quantify the model uncertainty that arises from using GSI chart for characterization of site-specific GSI in a transparent manner.

  19. Inferring gene dependency network specific to phenotypic alteration based on gene expression data and clinical information of breast cancer.

    Science.gov (United States)

    Zhou, Xionghui; Liu, Juan

    2014-01-01

    Although many methods have been proposed to reconstruct gene regulatory network, most of them, when applied in the sample-based data, can not reveal the gene regulatory relations underlying the phenotypic change (e.g. normal versus cancer). In this paper, we adopt phenotype as a variable when constructing the gene regulatory network, while former researches either neglected it or only used it to select the differentially expressed genes as the inputs to construct the gene regulatory network. To be specific, we integrate phenotype information with gene expression data to identify the gene dependency pairs by using the method of conditional mutual information. A gene dependency pair (A,B) means that the influence of gene A on the phenotype depends on gene B. All identified gene dependency pairs constitute a directed network underlying the phenotype, namely gene dependency network. By this way, we have constructed gene dependency network of breast cancer from gene expression data along with two different phenotype states (metastasis and non-metastasis). Moreover, we have found the network scale free, indicating that its hub genes with high out-degrees may play critical roles in the network. After functional investigation, these hub genes are found to be biologically significant and specially related to breast cancer, which suggests that our gene dependency network is meaningful. The validity has also been justified by literature investigation. From the network, we have selected 43 discriminative hubs as signature to build the classification model for distinguishing the distant metastasis risks of breast cancer patients, and the result outperforms those classification models with published signatures. In conclusion, we have proposed a promising way to construct the gene regulatory network by using sample-based data, which has been shown to be effective and accurate in uncovering the hidden mechanism of the biological process and identifying the gene signature for

  20. Automated size-specific CT dose monitoring program: Assessing variability in CT dose

    International Nuclear Information System (INIS)

    Christianson, Olav; Li Xiang; Frush, Donald; Samei, Ehsan

    2012-01-01

    Purpose: The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size-specific radiation dose monitoring program for CT and used this program to assess variability in size-adjusted effective dose from CT imaging. Methods: The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k-factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose-length product. The patient's thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size-adjusted effective dose (ED adj ). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one-month period and to analyze the variability in ED adj between scanner models and across institutions. Results: No significant difference was found between computer measurements of patient thickness and observer measurements (p= 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in ED adj that differed by up to 44% from effective dose estimates that were not

  1. Automated size-specific CT dose monitoring program: Assessing variability in CT dose

    Energy Technology Data Exchange (ETDEWEB)

    Christianson, Olav; Li Xiang; Frush, Donald; Samei, Ehsan [Clinical Imaging Physics Group, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 and Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Clinical Imaging Physics Group, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States) and Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Clinical Imaging Physics Group, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Department of Physics, Duke University, Durham, North Carolina 27710 (United States); and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States)

    2012-11-15

    Purpose: The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size-specific radiation dose monitoring program for CT and used this program to assess variability in size-adjusted effective dose from CT imaging. Methods: The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k-factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose-length product. The patient's thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size-adjusted effective dose (ED{sub adj}). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one-month period and to analyze the variability in ED{sub adj} between scanner models and across institutions. Results: No significant difference was found between computer measurements of patient thickness and observer measurements (p= 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in ED{sub adj} that differed by up to 44% from effective dose

  2. Stimulus-specific variability in color working memory with delayed estimation.

    Science.gov (United States)

    Bae, Gi-Yeul; Olkkonen, Maria; Allred, Sarah R; Wilson, Colin; Flombaum, Jonathan I

    2014-04-08

    Working memory for color has been the central focus in an ongoing debate concerning the structure and limits of visual working memory. Within this area, the delayed estimation task has played a key role. An implicit assumption in color working memory research generally, and delayed estimation in particular, is that the fidelity of memory does not depend on color value (and, relatedly, that experimental colors have been sampled homogeneously with respect to discriminability). This assumption is reflected in the common practice of collapsing across trials with different target colors when estimating memory precision and other model parameters. Here we investigated whether or not this assumption is secure. To do so, we conducted delayed estimation experiments following standard practice with a memory load of one. We discovered that different target colors evoked response distributions that differed widely in dispersion and that these stimulus-specific response properties were correlated across observers. Subsequent experiments demonstrated that stimulus-specific responses persist under higher memory loads and that at least part of the specificity arises in perception and is eventually propagated to working memory. Posthoc stimulus measurement revealed that rendered stimuli differed from nominal stimuli in both chromaticity and luminance. We discuss the implications of these deviations for both our results and those from other working memory studies.

  3. Instrument specific use-dependent plasticity shapes the anatomical properties of the corpus callosum

    DEFF Research Database (Denmark)

    Vollmann, Henning; Ragert, Patrick; Conde, Virginia

    2014-01-01

    Long-term musical expertise has been shown to be associated with a number of functional and structural brain changes, making it an attractive model for investigating use-dependent plasticity in humans. Physiological interhemispheric inhibition (IHI) as examined by transcranial magnetic stimulation......, the amount of IHI in pianists was comparable to that of non-musicians and there was no significant structure-function relationship. Our findings indicate instrument specific use-dependent plasticity in both functional (IHI) and structural (FA) connectivity of motor related brain regions in musicians....

  4. Temporal and sex-specific variability in Rhinoceros Auklet diet in the central California Current system

    Science.gov (United States)

    Carle, Ryan D.; Beck, Jessie N.; Calleri, David M.; Hester, Michelle M.

    2015-06-01

    We used stable isotopes (δ15N and δ13C) and compared prey provided to chicks by each sex to evaluate seasonal and sex-specific diets in Rhinoceros Auklets (Cerorhinca monocerata) in the central California Current system during 2012-2013. Mixing models indicated northern anchovy (Engraulis mordax) were important prey for adults during fall/winter and juvenile rockfishes (Sebastes spp.) were important prey during incubation both years. Adult trophic level increased between incubation and chick-rearing periods in both years. During 2012, δ15N and δ13C of chick-rearing males and females differed significantly; mixing models indicated that females ate more Pacific saury (Cololabis saira) and less market squid (Doryteuthis opalescens) than males. Likewise, females delivered significantly more Pacific saury and less market squid to chicks than males during 2012. Chick growth (g d- 1) and chick survival to fledging were significantly lower during 2012 than 2013, likely because chicks were fed lesser quality prey or fed less frequently in 2012. Lesser body mass of females during incubation in 2012 indicated sex-specific diet differences may have been related to female energetic constraints. The observed variability in Rhinoceros Auklet diet underscores the importance of managing multiple prey populations in this system so that generalist predators have sufficient resources through changing conditions.

  5. The Dependence of Cloud Particle Size on Non-Aerosol-Loading Related Variables

    Energy Technology Data Exchange (ETDEWEB)

    Shao, H.; Liu, G.

    2005-03-18

    An enhanced concentration of aerosol may increase the number of cloud drops by providing more cloud condensation nuclei (CCN), which in turn results in a higher cloud albedo at a constant cloud liquid water path. This process is often referred to as the aerosol indirect effect (AIE). Many in situ and remote sensing observations support this hypothesis (Ramanathan et al. 2001). However, satellite observed relations between aerosol concentration and cloud drop size are not always in agreement with the AIE. Based on global analysis of cloud effective radius (r{sub e}) and aerosol number concentration (N{sub a}) derived from satellite data, Sekiguchi et al. (2003) found that the correlations between the two variables can be either negative, or positive, or none, depending on the location of the clouds. They discovered that significantly negative r{sub e} - N{sub a} correlation can only be identified along coastal regions of the continents where abundant continental aerosols inflow from land, whereas Feingold et al. (2001) found that the response of r{sub e} to aerosol loading is the greatest in the region where aerosol optical depth ({tau}{sub a}) is the smallest. The reason for the discrepancy is likely due to the variations in cloud macroscopic properties such as geometrical thickness (Brenguier et al. 2003). Since r{sub e} is modified not only by aerosol but also by cloud geometrical thickness (H), the correlation between re and {tau}{sub a} actually reflects both the aerosol indirect effect and dependence of H. Therefore, discussing AIE based on the r{sub e}-{tau}{sub a} correlation without taking into account variations in cloud geometrical thickness may be misleading. This paper is motivated to extract aerosols' effect from overall effects using the independent measurements of cloud geometrical thickness, {tau}{sub a} and r{sub e}.

  6. Time-dependence in relativistic collisionless shocks: theory of the variable

    Energy Technology Data Exchange (ETDEWEB)

    Spitkovsky, A

    2004-02-05

    We describe results from time-dependent numerical modeling of the collisionless reverse shock terminating the pulsar wind in the Crab Nebula. We treat the upstream relativistic wind as composed of ions and electron-positron plasma embedded in a toroidal magnetic field, flowing radially outward from the pulsar in a sector around the rotational equator. The relativistic cyclotron instability of the ion gyrational orbit downstream of the leading shock in the electron-positron pairs launches outward propagating magnetosonic waves. Because of the fresh supply of ions crossing the shock, this time-dependent process achieves a limit-cycle, in which the waves are launched with periodicity on the order of the ion Larmor time. Compressions in the magnetic field and pair density associated with these waves, as well as their propagation speed, semi-quantitatively reproduce the behavior of the wisp and ring features described in recent observations obtained using the Hubble Space Telescope and the Chandra X-Ray Observatory. By selecting the parameters of the ion orbits to fit the spatial separation of the wisps, we predict the period of time variability of the wisps that is consistent with the data. When coupled with a mechanism for non-thermal acceleration of the pairs, the compressions in the magnetic field and plasma density associated with the optical wisp structure naturally account for the location of X-ray features in the Crab. We also discuss the origin of the high energy ions and their acceleration in the equatorial current sheet of the pulsar wind.

  7. Acetylation-Dependent Chromatin Reorganization by BRDT, a Testis-Specific Bromodomain-Containing Protein

    Science.gov (United States)

    Pivot-Pajot, Christophe; Caron, Cécile; Govin, Jérôme; Vion, Alexandre; Rousseaux, Sophie; Khochbin, Saadi

    2003-01-01

    The association between histone acetylation and replacement observed during spermatogenesis prompted us to consider the testis as a source for potential factors capable of remodelling acetylated chromatin. A systematic search of data banks for open reading frames encoding testis-specific bromodomain-containing proteins focused our attention on BRDT, a testis-specific protein of unknown function containing two bromodomains. BRDT specifically binds hyperacetylated histone H4 tail depending on the integrity of both bromodomains. Moreover, in somatic cells, the ectopic expression of BRDT triggered a dramatic reorganization of the chromatin only after induction of histone hyperacetylation by trichostatin A (TSA). We then defined critical domains of BRDT involved in its activity. Both bromodomains of BRDT, as well as flanking regions, were found indispensable for its histone acetylation-dependent remodelling activity. Interestingly, we also observed that recombinant BRDT was capable of inducing reorganization of the chromatin of isolated nuclei in vitro only when the nuclei were from TSA-treated cells. This assay also allowed us to show that the action of BRDT was ATP independent, suggesting a structural role for the protein in the remodelling of acetylated chromatin. This is the first demonstration of a large-scale reorganization of acetylated chromatin induced by a specific factor. PMID:12861021

  8. On the Interpretation of Instrumental Variables in the Presence of Specification Errors

    Directory of Open Access Journals (Sweden)

    P.A.V.B. Swamy

    2015-01-01

    Full Text Available The method of instrumental variables (IV and the generalized method of moments (GMM, and their applications to the estimation of errors-in-variables and simultaneous equations models in econometrics, require data on a sufficient number of instrumental variables that are both exogenous and relevant. We argue that, in general, such instruments (weak or strong cannot exist.

  9. Outer membrane targeting of Pseudomonas aeruginosa proteins shows variable dependence on the components of Bam and Lol machineries.

    Science.gov (United States)

    Hoang, Hanh H; Nickerson, Nicholas N; Lee, Vincent T; Kazimirova, Anastasia; Chami, Mohamed; Pugsley, Anthony P; Lory, Stephen

    2011-01-01

    In Gram-negative bacteria, the Lol and Bam machineries direct the targeting of lipidated and nonlipidated proteins, respectively, to the outer membrane (OM). Using Pseudomonas aeruginosa strains with depleted levels of specific Bam and Lol proteins, we demonstrated a variable dependence of different OM proteins on these targeting pathways. Reduction in the level of BamA significantly affected the ability of the β-barrel membrane protein OprF to localize to the OM, while the targeting of three secretins that are functionally related OM proteins was less affected (PilQ and PscC) or not at all affected (XcpQ). Depletion of LolB affected all lipoproteins examined and had a variable effect on the nonlipidated proteins. While the levels of OprF, PilQ, and PscC were significantly reduced by LolB depletion, XcpQ was unaffected and was correctly localized to the OM. These results suggest that certain β-barrel proteins such as OprF primarily utilize the complete Bam machinery. The Lol machinery participates in the OM targeting of secretins to variable degrees, likely through its involvement in the assembly of lipidated Bam components. XcpQ, but not PilQ or PscC, was shown to assemble spontaneously into liposomes as multimers. This work raises the possibility that there is a gradient of utilization of Bam and Lol insertion and targeting machineries. Structural features of individual proteins, including their β-barrel content, may determine the propensity of these proteins for folding (or misfolding) during periplasmic transit and OM insertion, thereby influencing the extent of utilization of the Bam targeting machinery, respectively. Targeting of lipidated and nonlipidated proteins to the outer membrane (OM) compartment in Gram-negative bacteria involves the transfer across the periplasm utilizing the Lol and Bam machineries, respectively. We show that depletion of Bam and Lol components in Pseudomonas aeruginosa does not lead to a general OM protein translocation defect

  10. Alaskan soil carbon stocks: spatial variability and dependence on environmental factors

    Directory of Open Access Journals (Sweden)

    U. Mishra

    2012-09-01

    Full Text Available The direction and magnitude of soil organic carbon (SOC changes in response to climate change depend on the spatial and vertical distributions of SOC. We estimated spatially resolved SOC stocks from surface to C horizon, distinguishing active-layer and permafrost-layer stocks, based on geospatial analysis of 472 soil profiles and spatially referenced environmental variables for Alaska. Total Alaska state-wide SOC stock was estimated to be 77 Pg, with 61% in the active-layer, 27% in permafrost, and 12% in non-permafrost soils. Prediction accuracy was highest for the active-layer as demonstrated by highest ratio of performance to deviation (1.5. Large spatial variability was predicted, with whole-profile, active-layer, and permafrost-layer stocks ranging from 1–296 kg C m−2, 2–166 kg m−2, and 0–232 kg m−2, respectively. Temperature and soil wetness were found to be primary controllers of whole-profile, active-layer, and permafrost-layer SOC stocks. Secondary controllers, in order of importance, were found to be land cover type, topographic attributes, and bedrock geology. The observed importance of soil wetness rather than precipitation on SOC stocks implies that the poor representation of high-latitude soil wetness in Earth system models may lead to large uncertainty in predicted SOC stocks under future climate change scenarios. Under strict caveats described in the text and assuming temperature changes from the A1B Intergovernmental Panel on Climate Change emissions scenario, our geospatial model indicates that the equilibrium average 2100 Alaska active-layer depth could deepen by 11 cm, resulting in a thawing of 13 Pg C currently in permafrost. The equilibrium SOC loss associated with this warming would be highest under continuous permafrost (31%, followed by discontinuous (28%, isolated (24.3%, and sporadic (23.6% permafrost areas. Our high-resolution mapping of soil carbon stock reveals the

  11. Correlation between maximum isometric strength variables and specific performance of Brazilian military judokas

    Directory of Open Access Journals (Sweden)

    Michel Moraes Gonçalves

    2017-06-01

    Full Text Available It was our objective to correlate specific performance in the Special Judo Fitness Test (SJFT and the maximum isometric handgrip (HGSMax, scapular traction (STSMax and lumbar traction (LTSMax strength tests in military judo athletes. Twenty-two military athletes from the judo team of the Brazilian Navy Almirante Alexandrino Instruction Centre, with average age of 26.14 ± 3.31 years old, and average body mass of 83.23 ± 14.14 kg participated in the study. Electronic dynamometry tests for HGSMax, STSMax and LTSMax were conducted. Then, after approximately 1 hour-interval, the SJFT protocol was applied. All variables were adjusted to the body mass of the athletes. Pearson correlation coefficient for statistical analysis was used. The results showed moderate negative correlation between the SJFT index and STSMax (r= -0.550, p= 0.008, strong negative correlations between the SJFT index and HGSMax (r= -0.706, p< 0.001, SJFT index and LTSMax (r= -0.721; p= 0.001, besides the correlation between the sum of the three maximum isometric strength tests and the SJFT index (r= -0.786, p< 0.001. This study concludes that negative correlations occur between the SJFT index and maximum isometric handgrip, shoulder and lumbar traction strength and the sum of the three maximum isometric strength tests in military judokas.

  12. MAPA distinguishes genotype-specific variability of highly similar regulatory protein isoforms in potato tuber.

    Science.gov (United States)

    Hoehenwarter, Wolfgang; Larhlimi, Abdelhalim; Hummel, Jan; Egelhofer, Volker; Selbig, Joachim; van Dongen, Joost T; Wienkoop, Stefanie; Weckwerth, Wolfram

    2011-07-01

    Mass Accuracy Precursor Alignment is a fast and flexible method for comparative proteome analysis that allows the comparison of unprecedented numbers of shotgun proteomics analyses on a personal computer in a matter of hours. We compared 183 LC-MS analyses and more than 2 million MS/MS spectra and could define and separate the proteomic phenotypes of field grown tubers of 12 tetraploid cultivars of the crop plant Solanum tuberosum. Protein isoforms of patatin as well as other major gene families such as lipoxygenase and cysteine protease inhibitor that regulate tuber development were found to be the primary source of variability between the cultivars. This suggests that differentially expressed protein isoforms modulate genotype specific tuber development and the plant phenotype. We properly assigned the measured abundance of tryptic peptides to different protein isoforms that share extensive stretches of primary structure and thus inferred their abundance. Peptides unique to different protein isoforms were used to classify the remaining peptides assigned to the entire subset of isoforms based on a common abundance profile using multivariate statistical procedures. We identified nearly 4000 proteins which we used for quantitative functional annotation making this the most extensive study of the tuber proteome to date.

  13. Design of a High Temperature Radiator for the Variable Specific Impulse Magnetoplasma Rocket

    Science.gov (United States)

    Sheth, Rubik B.; Ungar, Eugene K.; Chambliss, Joe P.

    2012-01-01

    The Variable Specific Impulse Magnetoplasma Rocket (VASIMR), currently under development by Ad Astra Rocket Company (Webster, TX), is a unique propulsion system that could change the way space propulsion is performed. VASIMR's efficiency, when compared to that of a conventional chemical rocket, reduces the propellant needed for exploration missions by a factor of 10. Currently plans include flight tests of a 200 kW VASIMR system, titled VF-200, on the International Space Station (ISS). The VF-200 will consist of two 100 kW thruster units packaged together in one engine bus. Each thruster core generates 27 kW of waste heat during its 15 minute firing time. The rocket core will be maintained between 283 and 573 K by a pumped thermal control loop. The design of a high temperature radiator is a unique challenge for the vehicle design. This paper will discuss the path taken to develop a steady state and transient-based radiator design. The paper will describe the radiator design option selected for the VASIMR thermal control system for use on ISS, and how the system relates to future exploration vehicles.

  14. Design Analysis of a High Temperature Radiator for the Variable Specific Impulse Magnetoplasma Rocket (VASIMR)

    Science.gov (United States)

    Sheth, Rubik B.; Ungar, Eugene K.; Chambliss, Joe P.; Cassady, Leonard D.

    2011-01-01

    The Variable Specific Impulse Magnetoplasma Rocket (VASIMR), currently under development by Ad Astra Rocket Company, is a unique propulsion system that can potentially change the way space propulsion is performed. VASIMR's efficiency, when compared to that of a conventional chemical rocket, reduce propellant needed for exploration missions by a factor of 10. Currently plans include flight tests of a 200 kW VASIMR system, titled VF-200, on the International Space Station. The VF-200 will consist of two 100 kW thruster units packaged together in one engine bus. Each thruster unit has a unique heat rejection requirement of about 27 kW over a firing time of 15 minutes. In order to control rocket core temperatures, peak operating temperatures of about 300 C are expected within the thermal control loop. Design of a high temperature radiator is a unique challenge for the vehicle design. This paper will discuss the path taken to develop a steady state and transient based radiator design. The paper will describe radiator design options for the VASIMR thermal control system for use on ISS as well as future exploration vehicles.

  15. MIRU-VNTR allelic variability depends on Mycobacterium bovis clonal group identity.

    Science.gov (United States)

    Hauer, Amandine; Michelet, Lorraine; De Cruz, Krystel; Cochard, Thierry; Branger, Maxime; Karoui, Claudine; Henault, Sylvie; Biet, Franck; Boschiroli, María Laura

    2016-11-01

    The description of the population of M. bovis strains circulating in France from 1978 to 2013 has highlighted the discriminating power of the MLVA among predominant spoligotype groups. In the present study we aimed to characterize clonal groups via MLVA and to better understand the strain's population structure. MLVA was performed with eight MIRU-VNTR loci, most of them defined by the Venomyc European consortium. The discriminatory index of each MLVA loci was calculated for SB0120, SB0134, SB0121 and the "F4-family", the main spoligotype groups in France. Differences in global DI per spoligotype, but also by locus within each spoligotype, were observed, which strongly suggest the clonal complex nature of these major groups. These MLVA results were compared to those of other European countries where strain collections had been characterized (Spain, Portugal, Italy, Northern Ireland and Belgium). Overall, QUB 3232 and ETR D are respectively the most and the least discriminative loci, regardless of the strains geographical origin. However, marked DI differences are observed in the rest of the MIRU-VNTR loci, again highlighting that strain genetic variability in a country depends on the dominant existing clonal complexes. A web application for M. bovis, including spoligotyping and MIRU-VNTR typing data, was developed to allow inter-laboratory comparison of field isolates. In conclusion, combination of typing methods is required for M. bovis optimum discrimination and differentiation of groups of strains. Thus, the loci employed for MLVA in a country should be those which are the most discriminative for the clonal complexes which characterize their M. bovis population. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Age-dependent tissue-specific exposure of cell phone users

    International Nuclear Information System (INIS)

    Christ, Andreas; Gosselin, Marie-Christine; Kuehn, Sven; Kuster, Niels; Christopoulou, Maria

    2010-01-01

    The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

  17. Age-dependent tissue-specific exposure of cell phone users

    Energy Technology Data Exchange (ETDEWEB)

    Christ, Andreas; Gosselin, Marie-Christine; Kuehn, Sven; Kuster, Niels [Foundation for Research on Information Technologies in Society (IT' IS), Zeughausstr. 43, 8004 Zuerich (Switzerland); Christopoulou, Maria [National Technical University of Athens, School of Electrical and Computer Engineering, 9 Iroon Polytechniou Str., 15780 Athens (Greece)], E-mail: christ@itis.ethz.ch

    2010-04-07

    The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

  18. Nodal-dependent mesendoderm specification requires the combinatorial activities of FoxH1 and Eomesodermin.

    Directory of Open Access Journals (Sweden)

    Christopher E Slagle

    2011-05-01

    Full Text Available Vertebrate mesendoderm specification requires the Nodal signaling pathway and its transcriptional effector FoxH1. However, loss of FoxH1 in several species does not reliably cause the full range of loss-of-Nodal phenotypes, indicating that Nodal signals through additional transcription factors during early development. We investigated the FoxH1-dependent and -independent roles of Nodal signaling during mesendoderm patterning using a novel recessive zebrafish FoxH1 mutation called midway, which produces a C-terminally truncated FoxH1 protein lacking the Smad-interaction domain but retaining DNA-binding capability. Using a combination of gel shift assays, Nodal overexpression experiments, and genetic epistasis analyses, we demonstrate that midway more accurately represents a complete loss of FoxH1-dependent Nodal signaling than the existing zebrafish FoxH1 mutant schmalspur. Maternal-zygotic midway mutants lack notochords, in agreement with FoxH1 loss in other organisms, but retain near wild-type expression of markers of endoderm and various nonaxial mesoderm fates, including paraxial and intermediate mesoderm and blood precursors. We found that the activity of the T-box transcription factor Eomesodermin accounts for specification of these tissues in midway embryos. Inhibition of Eomesodermin in midway mutants severely reduces the specification of these tissues and effectively phenocopies the defects seen upon complete loss of Nodal signaling. Our results indicate that the specific combinations of transcription factors available for signal transduction play critical and separable roles in determining Nodal pathway output during mesendoderm patterning. Our findings also offer novel insights into the co-evolution of the Nodal signaling pathway, the notochord specification program, and the chordate branch of the deuterostome family of animals.

  19. Antigen-specific tolerance of human alpha1-antitrypsin induced by helper-dependent adenovirus.

    Science.gov (United States)

    Cerullo, V; McCormack, W; Seiler, M; Mane, V; Cela, R; Clarke, C; Rodgers, J R; Lee, B

    2007-12-01

    As efficient and less toxic virus-derived gene therapy vectors are developed, a pressing problem is to avoid immune response to the therapeutic gene product. Secreted therapeutic proteins potentially represent a special problem, as they are readily available to professional antigen-presenting cells throughout the body. Some studies suggest that immunity to serum proteins can be avoided in some mouse strains by using tissue-specific promoters. Here we show that expression of human alpha1-antitrypsin (AAT) was nonimmunogenic in the immune-responsive strain C3H/HeJ, when expressed from helper-dependent (HD) vectors using ubiquitous as well as tissue-specific promoters. Coadministration of less immunogenic HD vectors with an immunogenic first-generation vector failed to immunize, suggesting immune suppression rather than immune stealth. Indeed, mice primed with HD vectors were tolerant to immune challenge with hAAT emulsified in complete Freund's adjuvant. Such animals developed high-titer antibodies to coemulsified human serum albumin, showing that tolerance was antigen specific. AAT-specific T cell responses were depressed in tolerized animals, suggesting that tolerance affects both T and B cells. These results are consistent with models of high-dose tolerance of B cells and certain other suppressive mechanisms, and suggest that a high level of expression from HD vectors can be sufficient to induce specific immune tolerance to serum proteins.

  20. Dependence of the specific surface area of the nuclear fuel with the matrix oxidation

    International Nuclear Information System (INIS)

    Gomez, F.; Quinones, J.; Iglesias, E.; Rodriguez, N.

    2008-01-01

    This paper is focused on the study of the changes in the specific surface area measured using BET techniques. The objective is to obtain a relation between this parameter and the change in the matrix stoichiometry (i.e., oxidation increase). None of the actual models used for extrapolating the behaviour of the spent fuel matrix under repository conditions have included this dependence yet. In this work the specific surface area of different uranium oxide were measured using N 2 (g) and Kr(g). The starting material was UO 2+x (s) with a size powder distribution lower than 20 μm. The results included in this paper shown a strong dependence on specific surface area with the matrix stoichiometry, i.e., and increase of more than one order of magnitude (SUO 2 = 6 m 2 *g -1 and SU 3 O 8 = 16.07 m 2 *g -1 ). Furthermore, the particle size distribution measured as a function of the thermal treatment done shows changes on the powder size related to the changes observed in the uranium oxide stoichiometry. (authors)

  1. Field-orientation dependence of the specific heat of PrOs4Sb12

    International Nuclear Information System (INIS)

    Custers, Jeroen; Namai, Yukie; Tayama, Takashi; Sakakibara, Toshiro; Sugawara, Hitoshi; Aoki, Yuji; Sato, Hideyuki

    2006-01-01

    The superconducting (SC) gap of the Pr-based skutterudite PrOs 4 Sb 12 has been investigated by means of field-angle-dependent specific heat C(H,φ) experiments. At fixed temperatures, H was varied and rotated in the basal planes. A 4-fold oscillation of C(H,φ) is observed in the entire H-T SC phase diagram. The minima are located along the [100] directions suggesting the excistence of gap nodes or minima along these directions. The oscillation amplitude vertical bar A vertical bar becomes maximum at H/H c2 ∼0.3. Below, vertical bar A vertical bar->0. The temperature variation of vertical bar A vertical bar follows a quadratic dependence

  2. Comparing measured and modelled soil carbon: which site-specific variables are linked to high stability?

    Science.gov (United States)

    Robertson, Andy; Schipanski, Meagan; Ma, Liwang; Ahuja, Lajpat; McNamara, Niall; Smith, Pete; Davies, Christian

    2016-04-01

    Changes in soil carbon (C) stocks have been studied in depth over the last two decades, as net greenhouse gas (GHG) sinks are highlighted to be a partial solution to the causes of climate change. However, the stability of this soil C is often overlooked when measuring these changes. Ultimately a net sequestration in soils is far less beneficial if labile C is replacing more stable forms. To date there is no accepted framework for measuring soil C stability, and as a result there is considerable uncertainty associated with the simulated impacts of land management and land use change when using process-based systems models. However, a recent effort to equate measurable soil C fractions to model pools has generated data that help to assess the impacts of land management, and can ultimately help to reduce the uncertainty of model predictions. Our research compiles this existing fractionation data along with site metadata to create a simplistic statistical model able to quantify the relative importance of different site-specific conditions. Data was mined from 23 published studies and combined with original data to generate a dataset of 100+ land use change sites across Europe. For sites to be included they required soil C fractions isolated using the Zimmermann et al. (2007) method and specific site metadata (mean annual precipitation, MAP; mean annual temperature, MAT; soil pH; land use; altitude). Of the sites, 75% were used to develop a generalized linear mixed model (GLMM) to create coefficients where site parameters can be used to predict influence on the measured soil fraction C stocks. The remaining 25% of sites were used to evaluate uncertainty and validate this empirical model. Further, four of the aforementioned sites were used to simulate soil C dynamics using the RothC, DayCent and RZWQM2 models. A sensitivity analysis (4096 model runs for each variable applying Latin hypercube random sampling techniques) was then used to observe whether these models place

  3. Processing Incomplete Query Specifications in a Context-Dependent Reasoning Framework

    Directory of Open Access Journals (Sweden)

    Neli P. Zlatareva

    2013-04-01

    Full Text Available Search is the most prominent web service, which is about to change dramatically with the transition to the Semantic Web. Semantic Web applications are expected to deal with complex conjunctive queries, and not always such queries can be completely and precisely defined. Current Semantic Web reasoners built upon Description Logics have limited processing power in such environments. We discuss some of their limitations, and show how an alternative logical framework utilizing context-dependent rules can be extended to handle incomplete or imprecise query specifications.

  4. Size-Dependent Specific Surface Area of Nanoporous Film Assembled by Core-Shell Iron Nanoclusters

    Directory of Open Access Journals (Sweden)

    Jiji Antony

    2006-01-01

    Full Text Available Nanoporous films of core-shell iron nanoclusters have improved possibilities for remediation, chemical reactivity rate, and environmentally favorable reaction pathways. Conventional methods often have difficulties to yield stable monodispersed core-shell nanoparticles. We produced core-shell nanoclusters by a cluster source that utilizes combination of Fe target sputtering along with gas aggregations in an inert atmosphere at 7∘C. Sizes of core-shell iron-iron oxide nanoclusters are observed with transmission electron microscopy (TEM. The specific surface areas of the porous films obtained from Brunauer-Emmett-Teller (BET process are size-dependent and compared with the calculated data.

  5. Computational study to investigate effect of tonometer geometry and patient-specific variability on radial artery tonometry.

    Science.gov (United States)

    Singh, Pranjal; Choudhury, Mohammed Ikbal; Roy, Sitikantha; Prasad, Anamika

    2017-06-14

    Tonometry-based devices are valuable method for vascular function assessment and for measurement of blood pressure. However current design and calibration methods rely on simple models, neglecting key geometrical features, and anthropometric and property variability among patients. Understanding impact of these influences on tonometer measurement is thus essential for improving outcomes of current devices, and for proposing improved design. Towards this goal, we present a realistic computational model for tissue-device interaction using complete wrist section with hyperelastic material and frictional contact. Three different tonometry geometries were considered including a new design, and patient-specific influences incorporated via anthropometric and age-dependent tissue stiffness variations. The results indicated that the new design showed stable surface contact stress with minimum influence of the parameters analyzed. The computational predictions were validated with experimental data from a prototype based on the new design. Finally, we showed that the underlying mechanics of vascular unloading in tonometry to be fundamentally different from that of oscillatory method. Due to directional loading in tonometry, pulse amplitude maxima was observed to occur at a significantly lower compression level (around 31%) than previously reported, which can impact blood pressure calibration approaches based on maximum pulse pressure recordings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Extracellular vesicles have variable dose-dependent effects on cultured draining cells in the eye.

    Science.gov (United States)

    Tabak, Saray; Schreiber-Avissar, Sofia; Beit-Yannai, Elie

    2018-03-01

    The role of extracellular vesicles (EVs) as signal mediators has been described in many biological fields. How many EVs are needed to deliver the desired physiological signal is yet unclear. Using a normal trabecular meshwork (NTM) cell culture exposed to non-pigmented ciliary epithelium (NPCE)-derived EVs, a relevant model for studying the human ocular drainage system, we addressed the EVs dose-response effects on the Wnt signaling. The objective of the study was to investigate the dosing effects of NPCE-derived EVs on TM Wnt signaling. EVs were isolated by PEG 8000 method from NPCE and RPE cells (used as controls) conditioned media. Concentrations were determined by Tunable Resistive Pulse Sensing method. Various exosomes concentration were incubated with TM cells, for the determination of mRNA (β-Catenin, Axin2 and LEF1) and protein (β-Catenin, GSK-3β) expression using real-time quantitative PCR and Western blot, respectively. Exposure of NTM cells for 8 hrs to low EVs concentrations was associated with a significant decreased expression of β-Catenin, GSK-3β, as opposed to exposure to high exosomal concentrations. Pro-MMP9 and MMP9 activities were significantly enhanced in NTM cells treated with high EV concentrations of (X10) as compared to low EV concentrations of either NPCE- or RPE-derived EVs and to untreated control. Our data support the concept that EVs biological effects are concentration-dependent at their target site. Specifically in the present study, we described a general dose-response at the gene and MMPs activity and a different dose-response regarding key canonical Wnt proteins expression. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  7. The Relationship of Field Dependent/Independent Cognitive Styles, Stimuli Variability and Time Factor on Student Achievement.

    Science.gov (United States)

    Atang, Christopher I.

    The effects of black and white and color illustrations on student achievement were studied to investigate the relationships between cognitive styles and instructional design. Field dependence (FD) and field independence (FI) were chosen as the cognitive style variables. Subjects were 85 freshman students in the Iowa State University Psychology…

  8. Effects of heat transfer, friction and variable specific heats of working fluid on performance of an irreversible dual cycle

    International Nuclear Information System (INIS)

    Chen Lingen; Ge Yanlin; Sun Fengrui; Wu Chih

    2006-01-01

    The thermodynamic performance of an air standard dual cycle with heat transfer loss, friction like term loss and variable specific heats of working fluid is analyzed. The relations between the power output and the compression ratio, between the thermal efficiency and the compression ratio, as well as the optimal relation between power output and the efficiency of the cycle, are derived by detailed numerical examples. Moreover, the effects of variable specific heats of the working fluid and the friction like term loss on the irreversible cycle performance are analyzed. The results show that the effects of variable specific heats of working fluid and friction like term loss on the cycle performance are obvious, and they should be considered in practical cycle analysis. The results obtained in this paper may provide guidance for the design of practical internal combustion engines

  9. Performance of an Atkinson cycle with heat transfer, friction and variable specific-heats of the working fluid

    International Nuclear Information System (INIS)

    Ge Yanlin; Chen Lingen; Sun, Fengrui; Wu Chih

    2006-01-01

    The performance of an air standard Atkinson cycle with heat-transfer loss, friction-like term loss and variable specific-heats of the working fluid is analyzed using finite-time thermodynamics. The relations between the power output and the compression ratio, between the thermal efficiency and the compression ratio, as well as the optimal relation between the power output and the efficiency of the cycle are derived by detailed numerical examples. Moreover, the effects of variable specific-heats of the working fluid and the friction-like term loss on the irreversible cycle performance are analyzed. The results show that the effects of variable specific-heats of working fluid and friction-like term loss on the irreversible cycle performance should be considered in cycle analysis. The results obtained in this paper provide guidance for the design of Atkinson engines

  10. A randomized trial of female-specific cognitive behavior therapy for alcohol dependent women.

    Science.gov (United States)

    Epstein, Elizabeth E; McCrady, Barbara S; Hallgren, Kevin A; Cook, Sharon; Jensen, Noelle K; Hildebrandt, Thomas

    2018-02-01

    This study compared Female-Specific Cognitive Behavioral Therapy (FS-CBT) to evidence-based, gender-neutral CBT (GN-CBT; Epstein & McCrady, 2009) for women with alcohol use disorder (AUD). Women (N = 99) with AUD, mean age 48, were randomly assigned to 12 outpatient manual-guided sessions of FS-CBT (n = 44) or GN-CBT (n = 55). Women were assessed at baseline and 3, 9 and 15 months after baseline for drinking and for specific issues common among women with AUD. A FS-CBT protocol was developed that was discriminable on treatment integrity ratings from GN-CBT. No treatment condition differences were found in treatment engagement, changes in drinking, alcohol-related coping, abstinence self-efficacy, motivation to change, or constructs directly targeted in FS-CBT (sociotropy, autonomy, depression, anxiety). Women in both conditions were highly engaged and satisfied with treatment, and reported significant reductions in drinking and changes in desired directions for all other variables except social support for abstinence. In the year following treatment, women in the FS-CBT but not in the CBT condition reported an increase in percentage of abstainers in their social networks (0.69% per month, SE = 0.21, p = .002). The value and appeal of female-specific programming in AUD treatment has been established in the wider literature (Epstein & Menges, 2013), and the current study provides support for the use of the Female-Specific Cognitive Behavioral Therapy (FS-CBT) manual as an option that may yield outcomes similar to standard gender-neutral CBT for women with AUD. Future research should examine whether FS-CBT enhances treatment utilization for women. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  11. Time-Dependent Drug Administration in Hypertension and its Effect on Blood Pressure Variability

    Directory of Open Access Journals (Sweden)

    Magdás Annamária

    2017-06-01

    Full Text Available Background: Optimizing blood pressure variability seems to represent a new therapeutic target in the management of hypertension. It is emphasized that scheduling at least one antihypertensive agent at bedtime, has the ability to reduce blood pressure.

  12. Time-Dependent Drug Administration in Hypertension and its Effect on Blood Pressure Variability

    OpenAIRE

    Magdás Annamária; Podoleanu Cristian; Tusa Anna-Boróka; Găburoi Adina; Incze Alexandru

    2017-01-01

    Background: Optimizing blood pressure variability seems to represent a new therapeutic target in the management of hypertension. It is emphasized that scheduling at least one antihypertensive agent at bedtime, has the ability to reduce blood pressure.

  13. The Variability of Atmospheric Deuterium Brightness at Mars: Evidence for Seasonal Dependence

    Science.gov (United States)

    Mayyasi, Majd; Clarke, John; Bhattacharyya, Dolon; Deighan, Justin; Jain, Sonal; Chaffin, Michael; Thiemann, Edward; Schneider, Nick; Jakosky, Bruce

    2017-10-01

    The enhanced ratio of deuterium to hydrogen on Mars has been widely interpreted as indicating the loss of a large column of water into space, and the hydrogen content of the upper atmosphere is now known to be highly variable. The variation in the properties of both deuterium and hydrogen in the upper atmosphere of Mars is indicative of the dynamical processes that produce these species and propagate them to altitudes where they can escape the planet. Understanding the seasonal variability of D is key to understanding the variability of the escape rate of water from Mars. Data from a 15 month observing campaign, made by the Mars Atmosphere and Volatile Evolution Imaging Ultraviolet Spectrograph high-resolution echelle channel, are used to determine the brightness of deuterium as observed at the limb of Mars. The D emission is highly variable, with a peak in brightness just after southern summer solstice. The trends of D brightness are examined against extrinsic as well as intrinsic sources. It is found that the fluctuations in deuterium brightness in the upper atmosphere of Mars (up to 400 km), corrected for periodic solar variations, vary on timescales that are similar to those of water vapor fluctuations lower in the atmosphere (20-80 km). The observed variability in deuterium may be attributed to seasonal factors such as regional dust storm activity and subsequent circulation lower in the atmosphere.

  14. Manipulating the Lewis antigen specificity of the cholesterol-dependent cytolysin lectinolysin

    Directory of Open Access Journals (Sweden)

    Sara eLawrence

    2012-11-01

    Full Text Available The cholesterol-dependent cytolysins (CDCs attack cells by punching large holes in their membranes. Lectinolysin from Streptococcus mitis is unique among CDCs due to the presence of an N-terminal lectin domain that enhances the pore-forming activity of the toxin. We recently determined the crystal structures of the lectin domain in complex with various glycans. These structures revealed the molecular basis for the Lewis antigen specificity of the toxin. Based on this information we have used in silico molecular modelling to design a mutant toxin, which we predicted would increase its specificity for Lewis y, an antigen found on the surface of cancer cells. Surprisingly, we found by surface plasmon resonance binding experiments that the resultant mutant lectin domain exhibited higher specificity for Lewis b antigens instead. We then undertook comparative crystallographic and molecular dynamics simulation studies of the wild-type and mutant lectin domains to understand the molecular basis for the disparity between the theoretical and experimental results. The crystallographic results revealed that the net number of interactions between Lewis y and wild-type versus mutant was unchanged whereas there was a loss of a hydrogen bond between mutant and Lewis b compared to wild-type. In contrast, the molecular dynamics studies revealed that the Lewis b antigen spent more time in the binding pocket of the mutant compared to wild-type and the reverse was true for Lewis y. The results of these simulation studies are consistent with the conclusions drawn from the surface plasmon resonance studies. This work is part of a program to engineer lectinolysin so that it will target and kill specific cells in human diseases.

  15. Nitric oxide regulates input specificity of long-term depression and context dependence of cerebellar learning.

    Directory of Open Access Journals (Sweden)

    Hideaki Ogasawara

    2007-01-01

    Full Text Available Recent studies have shown that multiple internal models are acquired in the cerebellum and that these can be switched under a given context of behavior. It has been proposed that long-term depression (LTD of parallel fiber (PF-Purkinje cell (PC synapses forms the cellular basis of cerebellar learning, and that the presynaptically synthesized messenger nitric oxide (NO is a crucial "gatekeeper" for LTD. Because NO diffuses freely to neighboring synapses, this volume learning is not input-specific and brings into question the biological significance of LTD as the basic mechanism for efficient supervised learning. To better characterize the role of NO in cerebellar learning, we simulated the sequence of electrophysiological and biochemical events in PF-PC LTD by combining established simulation models of the electrophysiology, calcium dynamics, and signaling pathways of the PC. The results demonstrate that the local NO concentration is critical for induction of LTD and for its input specificity. Pre- and postsynaptic coincident firing is not sufficient for a PF-PC synapse to undergo LTD, and LTD is induced only when a sufficient amount of NO is provided by activation of the surrounding PFs. On the other hand, above-adequate levels of activity in nearby PFs cause accumulation of NO, which also allows LTD in neighboring synapses that were not directly stimulated, ruining input specificity. These findings lead us to propose the hypothesis that NO represents the relevance of a given context and enables context-dependent selection of internal models to be updated. We also predict sparse PF activity in vivo because, otherwise, input specificity would be lost.

  16. Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay.

    Science.gov (United States)

    Cui, Heying; Loftus, Kyle M; Noell, Crystal R; Solmaz, Sozanne R

    2018-05-03

    Cyclin-dependent kinase 1 (Cdk1) is a master controller for the cell cycle in all eukaryotes and phosphorylates an estimated 8 - 13% of the proteome; however, the number of identified targets for Cdk1, particularly in human cells is still low. The identification of Cdk1-specific phosphorylation sites is important, as they provide mechanistic insights into how Cdk1 controls the cell cycle. Cell cycle regulation is critical for faithful chromosome segregation, and defects in this complicated process lead to chromosomal aberrations and cancer. Here, we describe an in vitro kinase assay that is used to identify Cdk1-specific phosphorylation sites. In this assay, a purified protein is phosphorylated in vitro by commercially available human Cdk1/cyclin B. Successful phosphorylation is confirmed by SDS-PAGE, and phosphorylation sites are subsequently identified by mass spectrometry. We also describe purification protocols that yield highly pure and homogeneous protein preparations suitable for the kinase assay, and a binding assay for the functional verification of the identified phosphorylation sites, which probes the interaction between a classical nuclear localization signal (cNLS) and its nuclear transport receptor karyopherin α. To aid with experimental design, we review approaches for the prediction of Cdk1-specific phosphorylation sites from protein sequences. Together these protocols present a very powerful approach that yields Cdk1-specific phosphorylation sites and enables mechanistic studies into how Cdk1 controls the cell cycle. Since this method relies on purified proteins, it can be applied to any model organism and yields reliable results, especially when combined with cell functional studies.

  17. On history dependence of stress-strain diagrams and creep curves under variable repeated loading

    International Nuclear Information System (INIS)

    Gokhfeld, D.A.; Sadakov, O.S.; Martynenko, M.E.

    1979-01-01

    The ability of structural alloys to 'keep in memory' the loading prehistory becomes of special importance when inelastic variable repeated loading is considered. There are two main approaches to the development of the mathematical description of this phenomenon: the inclusion of hidden state variables in the incremental theory constitutive equations (a) and construction of proper hereditary functionals (b). In this respect the assumption that the 'memory' regarding the previous deformation history is due to structural nonhomogeneity of actual materials proves to be fruitful. (orig.)

  18. Cerebellum-specific and age-dependent expression of an endogenous retrovirus with intact coding potential

    Directory of Open Access Journals (Sweden)

    Itoh Takayuki

    2011-10-01

    Full Text Available Abstract Background Endogenous retroviruses (ERVs, including murine leukemia virus (MuLV type-ERVs (MuLV-ERVs, are presumed to occupy ~10% of the mouse genome. In this study, following the identification of a full-length MuLV-ERV by in silico survey of the C57BL/6J mouse genome, its distribution in different mouse strains and expression characteristics were investigated. Results Application of a set of ERV mining protocols identified a MuLV-ERV locus with full coding potential on chromosome 8 (named ERVmch8. It appears that ERVmch8 shares the same genomic locus with a replication-incompetent MuLV-ERV, called Emv2; however, it was not confirmed due to a lack of relevant annotation and Emv2 sequence information. The ERVmch8 sequence was more prevalent in laboratory strains compared to wild-derived strains. Among 16 different tissues of ~12 week-old female C57BL/6J mice, brain homogenate was the only tissue with evident expression of ERVmch8. Further ERVmch8 expression analysis in six different brain compartments and four peripheral neuronal tissues of C57BL/6J mice revealed no significant expression except for the cerebellum in which the ERVmch8 locus' low methylation status was unique compared to the other brain compartments. The ERVmch8 locus was found to be surrounded by genes associated with neuronal development and/or inflammation. Interestingly, cerebellum-specific ERVmch8 expression was age-dependent with almost no expression at 2 weeks and a plateau at 6 weeks. Conclusions The ecotropic ERVmch8 locus on the C57BL/6J mouse genome was relatively undermethylated in the cerebellum, and its expression was cerebellum-specific and age-dependent.

  19. Illicit drug use and abuse/dependence: modeling of two-stage variables using the CCC approach.

    Science.gov (United States)

    Agrawal, A; Neale, M C; Jacobson, K C; Prescott, C A; Kendler, K S

    2005-06-01

    Drug use and abuse/dependence are stages of a complex drug habit. Most genetically informative models that are fit to twin data examine drug use and abuse/dependence independent of each other. This poses an interesting question: for a multistage process, how can we partition the factors influencing each stage specifically from the factors that are common to both stages? We used a causal-common-contingent (CCC) model to partition the common and specific influences on drug use and abuse/dependence. Data on use and abuse/dependence of cannabis, cocaine, sedatives, stimulants and any illicit drug was obtained from male and female twin pairs. CCC models were tested individually for each sex and in a sex-equal model. Our results suggest that there is evidence for additive genetic, shared environmental and unique environmental influences that are common to illicit drug use and abuse/dependence. Furthermore, we found substantial evidence for factors that were specific to abuse/dependence. Finally, sexes could be equated for all illicit drugs. The findings of this study emphasize the need for models that can partition the sources of individual differences into common and stage-specific influences.

  20. Differences in kinematics of the support limb depends on specific movement tasks of take-off

    Directory of Open Access Journals (Sweden)

    Vladimír Hojka

    2016-06-01

    Full Text Available Background: Many sport activities are a sequence of jumps (running, jumping, hurdling etc.. Each jump flight phase is the result of the execution of the previous support phase. Objective: The goal of the research was to identify differences in adjustment of the support lower limb and differences in take-off kinematics in specific take-off movement task. Methods: 14 male athletes (22.6 ± 4.4 years; 182.4 ± 5.3 cm; 74.7 ± 6.2 kg took part in a laboratory experiment. Each athlete performed five different take-off movements (running, acceleration running - second step, long jump take-off, high jump take-off and take-off to the hurdle. System Qualisys was used to analyze the kinematics of the support limb. Dynamics of the support phase was monitored via force plate. ANOVA and Bonferroni post-hoc test were used to measure the significance of the differences between different take off tasks. Results: Dynamic characteristic showed significant differences in take-off (p < .001. This variability is caused by differences in kinematic parameters at the instant of touch-down, minimum joint angles and take-off. The most important finding was different variability in range of motion in eccentric or concentric phases of each jump. Vertically orientated jumps are terminated in a higher degree of extension. Horizontal take-off types are characterized by the highest ranges of motion especially in the ankle joint. Conclusions: The support lower limb compliance is adjusted to the required task, which is related to lower limb kinematics during the support phase. High range of motion in each joint refers to more compliant adjustment of the joint.

  1. Rifampicin-dependent antibodies bind a similar or identical epitope to glycoprotein IX-specific quinine-dependent antibodies

    NARCIS (Netherlands)

    Burgess, Janette K.; Lopez, Jose A.; Gaudry, Leonie E.; Chong, Beng H.

    2000-01-01

    The drug-dependent antibody of a patient with rifampicin-induced thrombocytopenia was characterized using the antigen-capture enzyme-linked immunosorbent assay (MAIPA assay), flow cytometry, and immunoprecipitation. The antibody was found to bind glycoprotein (GP) Ib-IX but not GPIIb-IIIa because

  2. Distance and Azimuthal Dependence of Ground‐Motion Variability for Unilateral Strike‐Slip Ruptures

    KAUST Repository

    Vyas, Jagdish Chandra; Mai, Paul Martin; Galis, Martin

    2016-01-01

    We investigate near‐field ground‐motion variability by computing the seismic wavefield for five kinematic unilateral‐rupture models of the 1992 Mw 7.3 Landers earthquake, eight simplified unilateral‐rupture models based on the Landers event, and a

  3. Phase dependence of transport-aperture coordination variability reveals control strategy of reach-to-grasp movements.

    Science.gov (United States)

    Rand, Miya K; Shimansky, Y P; Hossain, Abul B M I; Stelmach, George E

    2010-11-01

    Based on an assumption of movement control optimality in reach-to-grasp movements, we have recently developed a mathematical model of transport-aperture coordination (TAC), according to which the hand-target distance is a function of hand velocity and acceleration, aperture magnitude, and aperture velocity and acceleration (Rand et al. in Exp Brain Res 188:263-274, 2008). Reach-to-grasp movements were performed by young adults under four different reaching speeds and two different transport distances. The residual error magnitude of fitting the above model to data across different trials and subjects was minimal for the aperture-closure phase, but relatively much greater for the aperture-opening phase, indicating considerable difference in TAC variability between those phases. This study's goal is to identify the main reasons for that difference and obtain insights into the control strategy of reach-to-grasp movements. TAC variability within the aperture-opening phase of a single trial was found minimal, indicating that TAC variability between trials was not due to execution noise, but rather a result of inter-trial and inter-subject variability of motor plan. At the same time, the dependence of the extent of trial-to-trial variability of TAC in that phase on the speed of hand transport was sharply inconsistent with the concept of speed-accuracy trade-off: the lower the speed, the larger the variability. Conversely, the dependence of the extent of TAC variability in the aperture-closure phase on hand transport speed was consistent with that concept. Taking into account recent evidence that the cost of neural information processing is substantial for movement planning, the dependence of TAC variability in the aperture-opening phase on task performance conditions suggests that it is not the movement time that the CNS saves in that phase, but the cost of neuro-computational resources and metabolic energy required for TAC regulation in that phase. Thus, the CNS

  4. A specific pharmacophore model of sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors.

    Science.gov (United States)

    Tang, Chunlei; Zhu, Xiaoyun; Huang, Dandan; Zan, Xin; Yang, Baowei; Li, Ying; Du, Xiaoyong; Qian, Hai; Huang, Wenlong

    2012-06-01

    Sodium-dependent glucose co-transporter 2 (SGLT2) plays a pivotal role in maintaining glucose equilibrium in the human body, emerging as one of the most promising targets for the treatment of diabetes mellitus type 2. Pharmacophore models of SGLT2 inhibitors have been generated with a training set of 25 SGLT2 inhibitors using Discovery Studio V2.1. The best hypothesis (Hypo1(SGLT2)) contains one hydrogen bond donor, five excluded volumes, one ring aromatic and three hydrophobic features, and has a correlation coefficient of 0.955, cost difference of 68.76, RMSD of 0.85. This model was validated by test set, Fischer randomization test and decoy set methods. The specificity of Hypo1(SGLT2) was evaluated. The pharmacophore features of Hypo1(SGLT2) were different from the best pharmacophore model (Hypo1(SGLT1)) of SGLT1 inhibitors we developed. Moreover, Hypo1(SGLT2) could effectively distinguish selective inhibitors of SGLT2 from those of SGLT1. These results indicate that a highly predictive and specific pharmacophore model of SGLT2 inhibitors has been successfully obtained. Then Hypo1(SGLT2) was used as a 3D query to screen databases including NCI and Maybridge for identifying new inhibitors of SGLT2. The hit compounds were subsequently subjected to filtering by Lipinski's rule of five. And several compounds selected from the top ranked hits have been suggested for further experimental assay studies.

  5. Impaired fear memory specificity associated with deficient endocannabinoid-dependent long-term plasticity.

    Science.gov (United States)

    Lovelace, Jonathan W; Vieira, Philip A; Corches, Alex; Mackie, Ken; Korzus, Edward

    2014-06-01

    In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC) in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic long-term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.

  6. Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota

    Science.gov (United States)

    Chung, Hachung; Pamp, Sünje J.; Hill, Jonathan A.; Surana, Neeraj K.; Edelman, Sanna M.; Troy, Erin B.; Reading, Nicola C.; Villablanca, Eduardo J.; Wang, Sen; Mora, Jorge R.; Umesaki, Yoshinori; Mathis, Diane; Benoist, Christophe; Relman, David A.; Kasper, Dennis L.

    2012-01-01

    SUMMARY Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4+ and CD8+ T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression–all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system. PMID:22726443

  7. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Tramontano, Anna

    2011-01-01

    of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface

  8. Variable rate application of nematicides on cotton fields: A promising site-specific management strategy.

    Science.gov (United States)

    Field tests were conducted to determine if differences in response to nematicide application (i.e., root-knot nematode (RKN) population levels, cotton yield, and profitability) occurred among RKN management zones (MZ). The MZ were delineated using variables related to soil texture, including appare...

  9. Context-dependent activation of reduced autobiographical memory specificity as an avoidant coping style.

    Science.gov (United States)

    Debeer, Elise; Raes, Filip; Williams, J Mark G; Hermans, Dirk

    2011-12-01

    According to the affect-regulation hypothesis (Williams et al., 2007), reduced autobiographical memory specificity (rAMS) or overgeneral memory (OGM) might be considered a cognitive avoidance strategy; that is, people learn to avoid the emotionally painful consequences associated with the retrieval of specific negative memories. Based on this hypothesis, one would predict significant negative associations between AMS and avoidant coping. However, studies investigating this prediction have led to equivocal results. In the present study we tested a possible explanation for these contradictory findings. It was hypothesized that rAMS (in part) reflects an avoidant coping strategy, which might only become apparent under certain conditions, that is, conditions that signal the possibility of 'danger.' To test this hypothesis, we assessed AMS and behavioral avoidance but experimentally manipulated the instructions. In the neutral condition, two parallel versions of the Autobiographical Memory Test (AMT) were presented under neutral instructions. In the threat condition, the first AMT was presented under neutral instructions, while the second AMT was presented under 'threat instructions.' Results showed no significant correlations between avoidance and OGM under neutral conditions but significant and markedly stronger correlations under threat conditions, with more avoidance being associated with fewer specific and more categoric memories. In addition, high avoiders showed a stronger reduction in AMS in the threat condition as compared with the neutral condition, while low avoiders showed no such difference between conditions. The data confirm that OGM can be considered as part of a broader avoidant coping style. However, more importantly, they show that, at least in nonclinical individuals, the activation of this coping style may depend on the context. (c) 2011 APA, all rights reserved.

  10. Morphometric variability of mandible linear characteristics depending on level of teeth alveolus position

    Directory of Open Access Journals (Sweden)

    Olga Yu. Aleshkina

    2017-05-01

    Results and Conclusion ― The highest altitude was marked at levels of incisors and 3rd molar, the smallest one – at level of 1st and 2nd molars; maximum mandible thickness was defined at level of 2nd molar, minimum – at levels of canine and 1st – 2nd premolars on both sides of mandible; average thickness was revealed at levels of incisors, 1st and 2nd molars and had the same statistical values. Bilateral variability of thickness was significantly dominating on the right side and only at levels of 1st – 2nd premolars and 1st molar. Average values of altitude and thickness from both sides of mandible and at all levels had medium degree of variability.

  11. Scale-dependent spatial variability in peatland lead pollution in the southern Pennines, UK

    International Nuclear Information System (INIS)

    Rothwell, James J.; Evans, Martin G.; Lindsay, John B.; Allott, Timothy E.H.

    2007-01-01

    Increasingly, within-site and regional comparisons of peatland lead pollution have been undertaken using the inventory approach. The peatlands of the Peak District, southern Pennines, UK, have received significant atmospheric inputs of lead over the last few hundred years. A multi-core study at three peatland sites in the Peak District demonstrates significant within-site spatial variability in industrial lead pollution. Stochastic simulations reveal that 15 peat cores are required to calculate reliable lead inventories at the within-site and within-region scale for this highly polluted area of the southern Pennines. Within-site variability in lead pollution is dominant at the within-region scale. The study demonstrates that significant errors may be associated with peatland lead inventories at sites where only a single peat core has been used to calculate an inventory. Meaningful comparisons of lead inventories at the regional or global scale can only be made if the within-site variability of lead pollution has been quantified reliably. - Multiple peat cores are required for accurate peatland Pb inventories

  12. Scale-dependent spatial variability in peatland lead pollution in the southern Pennines, UK.

    Science.gov (United States)

    Rothwell, James J; Evans, Martin G; Lindsay, John B; Allott, Timothy E H

    2007-01-01

    Increasingly, within-site and regional comparisons of peatland lead pollution have been undertaken using the inventory approach. The peatlands of the Peak District, southern Pennines, UK, have received significant atmospheric inputs of lead over the last few hundred years. A multi-core study at three peatland sites in the Peak District demonstrates significant within-site spatial variability in industrial lead pollution. Stochastic simulations reveal that 15 peat cores are required to calculate reliable lead inventories at the within-site and within-region scale for this highly polluted area of the southern Pennines. Within-site variability in lead pollution is dominant at the within-region scale. The study demonstrates that significant errors may be associated with peatland lead inventories at sites where only a single peat core has been used to calculate an inventory. Meaningful comparisons of lead inventories at the regional or global scale can only be made if the within-site variability of lead pollution has been quantified reliably.

  13. Natural variability of biochemical biomarkers in the macro-zoobenthos: Dependence on life stage and environmental factors.

    Science.gov (United States)

    Scarduelli, Lucia; Giacchini, Roberto; Parenti, Paolo; Migliorati, Sonia; Di Brisco, Agnese Maria; Vighi, Marco

    2017-11-01

    Biomarkers are widely used in ecotoxicology as indicators of exposure to toxicants. However, their ability to provide ecologically relevant information remains controversial. One of the major problems is understanding whether the measured responses are determined by stress factors or lie within the natural variability range. In a previous work, the natural variability of enzymatic levels in invertebrates sampled in pristine rivers was proven to be relevant across both space and time. In the present study, the experimental design was improved by considering different life stages of the selected taxa and by measuring more environmental parameters. The experimental design considered sampling sites in 2 different rivers, 8 sampling dates covering the whole seasonal cycle, 4 species from 3 different taxonomic groups (Plecoptera, Perla grandis; Ephemeroptera, Baetis alpinus and Epeorus alpicula; Tricoptera, Hydropsyche pellucidula), different life stages for each species, and 4 enzymes (acetylcholinesterase, glutathione S-transferase, alkaline phosphatase, and catalase). Biomarker levels were related to environmental (physicochemical) parameters to verify any kind of dependence. Data were statistically elaborated using hierarchical multilevel Bayesian models. Natural variability was found to be relevant across both space and time. The results of the present study proved that care should be paid when interpreting biomarker results. Further research is needed to better understand the dependence of the natural variability on environmental parameters. Environ Toxicol Chem 2017;36:3158-3167. © 2017 SETAC. © 2017 SETAC.

  14. A residue-specific shift in stability and amyloidogenicity of antibody variable domains.

    Science.gov (United States)

    Nokwe, Cardine N; Zacharias, Martin; Yagi, Hisashi; Hora, Manuel; Reif, Bernd; Goto, Yuji; Buchner, Johannes

    2014-09-26

    Variable (V) domains of antibodies are essential for antigen recognition by our adaptive immune system. However, some variants of the light chain V domains (VL) form pathogenic amyloid fibrils in patients. It is so far unclear which residues play a key role in governing these processes. Here, we show that the conserved residue 2 of VL domains is crucial for controlling its thermodynamic stability and fibril formation. Hydrophobic side chains at position 2 stabilize the domain, whereas charged residues destabilize and lead to amyloid fibril formation. NMR experiments identified several segments within the core of the VL domain to be affected by changes in residue 2. Furthermore, molecular dynamic simulations showed that hydrophobic side chains at position 2 remain buried in a hydrophobic pocket, and charged side chains show a high flexibility. This results in a predicted difference in the dissociation free energy of ∼10 kJ mol(-1), which is in excellent agreement with our experimental values. Interestingly, this switch point is found only in VL domains of the κ family and not in VLλ or in VH domains, despite a highly similar domain architecture. Our results reveal novel insight into the architecture of variable domains and the prerequisites for formation of amyloid fibrils. This might also contribute to the rational design of stable variable antibody domains. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Assessment of variability in the hydrological cycle of the Loess Plateau, China: examining dependence structures of hydrological processes

    Science.gov (United States)

    Guo, A.; Wang, Y.

    2017-12-01

    Investigating variability in dependence structures of hydrological processes is of critical importance for developing an understanding of mechanisms of hydrological cycles in changing environments. In focusing on this topic, present work involves the following: (1) identifying and eliminating serial correlation and conditional heteroscedasticity in monthly streamflow (Q), precipitation (P) and potential evapotranspiration (PE) series using the ARMA-GARCH model (ARMA: autoregressive moving average; GARCH: generalized autoregressive conditional heteroscedasticity); (2) describing dependence structures of hydrological processes using partial copula coupled with the ARMA-GARCH model and identifying their variability via copula-based likelihood-ratio test method; and (3) determining conditional probability of annual Q under different climate scenarios on account of above results. This framework enables us to depict hydrological variables in the presence of conditional heteroscedasticity and to examine dependence structures of hydrological processes while excluding the influence of covariates by using partial copula-based ARMA-GARCH model. Eight major catchments across the Loess Plateau (LP) are used as study regions. Results indicate that (1) The occurrence of change points in dependence structures of Q and P (PE) varies across the LP. Change points of P-PE dependence structures in all regions almost fully correspond to the initiation of global warming, i.e., the early 1980s. (3) Conditional probabilities of annual Q under various P and PE scenarios are estimated from the 3-dimensional joint distribution of (Q, P and PE) based on the above change points. These findings shed light on mechanisms of the hydrological cycle and can guide water supply planning and management, particularly in changing environments.

  16. Time-dependent inelastic analysis of metallic media using constitutive relations with state variables

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, V; Mukherjee, S [Cornell Univ., Ithaca, N.Y. (USA)

    1977-03-01

    A computational technique in terms of stress, strain and displacement rates is presented for the solution of boundary value problems for metallic structural elements at uniform elevated temperatures subjected to time varying loads. This method can accommodate any number of constitutive relations with state variables recently proposed by other researchers to model the inelastic deformation of metallic media at elevated temperatures. Numerical solutions are obtained for several structural elements subjected to steady loads. The constitutive relations used for these numerical solutions are due to Hart. The solutions are discussed in the context of the computational scheme and Hart's theory.

  17. SECOND ORDER LEAST SQUARE ESTIMATION ON ARCH(1 MODEL WITH BOX-COX TRANSFORMED DEPENDENT VARIABLE

    Directory of Open Access Journals (Sweden)

    Herni Utami

    2014-03-01

    Full Text Available Box-Cox transformation is often used to reduce heterogeneity and to achieve a symmetric distribution of response variable. In this paper, we estimate the parameters of Box-Cox transformed ARCH(1 model using second-order leastsquare method and then we study the consistency and asymptotic normality for second-order least square (SLS estimators. The SLS estimation was introduced byWang (2003, 2004 to estimate the parameters of nonlinear regression models with independent and identically distributed errors

  18. THE DIFFERENCES IN MORAL, GROUP IDENTITY AND THE PERCON’S VARIABILITY DEPENDING ON THE EDUCATION

    Directory of Open Access Journals (Sweden)

    Irina Aleksandrobna Kolinichenko

    2017-06-01

    Results. The results of the study have revealed the dominance of all specified assessment parameters in the group of test subjects with incomplete higher education: higher level of moral development in all dilemmas (the opposition of life values (compassion and following the law, self-interest – the interests of the city (law, business (benefit and law, personal interests (career and the freedom of another person, except for the dilemma of the opposition between the interests of a majority and a single person. The differences have also been revealed between the two groups of test subjects according to the group identity, group variability, the desirability of the common categories of identity.

  19. Dependence of conductivity on thickness within the variable-range hopping regime for Coulomb glasses

    Directory of Open Access Journals (Sweden)

    M. Caravaca

    Full Text Available In this paper, we provide some computational evidence concerning the dependence of conductivity on the system thickness for Coulomb glasses. We also verify the Efros–Shklovskii law and deal with the calculation of its characteristic parameter as a function of the thickness. Our results strengthen the link between theoretical and experimental fields. Keywords: Coulomb glass, Conductivity, Density of states, Efros–Shklovskii law

  20. Temperature-dependent behaviours are genetically variable in the nematode Caenorhabditis briggsae.

    Science.gov (United States)

    Stegeman, Gregory W; de Mesquita, Matthew Bueno; Ryu, William S; Cutter, Asher D

    2013-03-01

    Temperature-dependent behaviours in Caenorhabditis elegans, such as thermotaxis and isothermal tracking, are complex behavioural responses that integrate sensation, foraging and learning, and have driven investigations to discover many essential genetic and neural pathways. The ease of manipulation of the Caenorhabditis model system also has encouraged its application to comparative analyses of phenotypic evolution, particularly contrasts of the classic model C. elegans with C. briggsae. And yet few studies have investigated natural genetic variation in behaviour in any nematode. Here we measure thermotaxis and isothermal tracking behaviour in genetically distinct strains of C. briggsae, further motivated by the latitudinal differentiation in C. briggsae that is associated with temperature-dependent fitness differences in this species. We demonstrate that C. briggsae performs thermotaxis and isothermal tracking largely similar to that of C. elegans, with a tendency to prefer its rearing temperature. Comparisons of these behaviours among strains reveal substantial heritable natural variation within each species that corresponds to three general patterns of behavioural response. However, intraspecific genetic differences in thermal behaviour often exceed interspecific differences. These patterns of temperature-dependent behaviour motivate further development of C. briggsae as a model system for dissecting the genetic underpinnings of complex behavioural traits.

  1. Performance prediction for silicon photonics integrated circuits with layout-dependent correlated manufacturing variability.

    Science.gov (United States)

    Lu, Zeqin; Jhoja, Jaspreet; Klein, Jackson; Wang, Xu; Liu, Amy; Flueckiger, Jonas; Pond, James; Chrostowski, Lukas

    2017-05-01

    This work develops an enhanced Monte Carlo (MC) simulation methodology to predict the impacts of layout-dependent correlated manufacturing variations on the performance of photonics integrated circuits (PICs). First, to enable such performance prediction, we demonstrate a simple method with sub-nanometer accuracy to characterize photonics manufacturing variations, where the width and height for a fabricated waveguide can be extracted from the spectral response of a racetrack resonator. By measuring the spectral responses for a large number of identical resonators spread over a wafer, statistical results for the variations of waveguide width and height can be obtained. Second, we develop models for the layout-dependent enhanced MC simulation. Our models use netlist extraction to transfer physical layouts into circuit simulators. Spatially correlated physical variations across the PICs are simulated on a discrete grid and are mapped to each circuit component, so that the performance for each component can be updated according to its obtained variations, and therefore, circuit simulations take the correlated variations between components into account. The simulation flow and theoretical models for our layout-dependent enhanced MC simulation are detailed in this paper. As examples, several ring-resonator filter circuits are studied using the developed enhanced MC simulation, and statistical results from the simulations can predict both common-mode and differential-mode variations of the circuit performance.

  2. Sex-Specific Effects of Unpredictable Variable Prenatal Stress: Implications for Mammalian Developmental Programming During Spaceflight

    Science.gov (United States)

    Talyansky, Y.; Moyer, E. L.; Oijala, E.; Baer, L. A.; Ronca, A. E.

    2016-01-01

    During adaptation to the microgravity environment, adult mammals experience stress mediated by the Hypothalamic-Pituitary-Adrenal axis. In our previous studies of pregnant rats exposed to 2-g hypergravity via centrifugation, we reported decreased corticosterone and increased body mass and leptin in adult male, but not female, offspring. In this study, we utilized Unpredictable Variable Prenatal Stress to simulate the stressors of spaceflight by exposing dams to different stressors. Stress response modulation occurs via both positive and negative feedback in the hypothalamus, anterior pituitary gland, and adrenal cortex resulting in the differential release of corticosterone (CORT), a murine analog to human cortisol.

  3. Technical specifications of variable speed motors for negative pressure control in hot cell area

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seon Duk; Bang, H. S.; Cho, W. K

    2002-01-01

    Hot cells are the facilities for handling the high radioactive materials and various R and D activities are performed using hot cells. Therefore the control of air flow in hot cell area is very important technology and it is started with the variable speed motor(VSM) controlling the air handling system in that area. This report describes various technical aspects of VS motors and will be useful for understanding the practical technologies of VS motors and also for optimization of the negative pressure controls in hot cell area.

  4. Cell Type-Specific Manipulation with GFP-Dependent Cre Recombinase

    Science.gov (United States)

    Tang, Jonathan C Y; Rudolph, Stephanie; Dhande, Onkar S; Abraira, Victoria E; Choi, Seungwon; Lapan, Sylvain; Drew, Iain R; Drokhlyansky, Eugene; Huberman, Andrew D; Regehr, Wade G; Cepko, Constance L

    2016-01-01

    Summary There are many transgenic GFP reporter lines that allow visualization of specific populations of cells. Using such lines for functional studies requires a method that transforms GFP into a molecule that enables genetic manipulation. Here we report the creation of a method that exploits GFP for gene manipulation, Cre Recombinase Dependent on GFP (CRE-DOG), a split component system that uses GFP and its derivatives to directly induce Cre/loxP recombination. Using plasmid electroporation and AAV viral vectors, we delivered CRE-DOG to multiple GFP mouse lines, leading to effective recombination selectively in GFP-labeled cells. Further, CRE-DOG enabled optogenetic control of these neurons. Beyond providing a new set of tools for manipulation of gene expression selectively in GFP+ cells, we demonstrate that GFP can be used to reconstitute the activity of a protein not known to have a modular structure, suggesting that this strategy might be applicable to a wide range of proteins. PMID:26258682

  5. Parent-of-origin dependent gene-specific knock down in mouse embryos

    International Nuclear Information System (INIS)

    Iqbal, Khursheed; Kues, Wilfried A.; Niemann, Heiner

    2007-01-01

    In mice hemizygous for the Oct4-GFP transgene, the F1 embryos show parent-of-origin dependent expression of the marker gene. F1 embryos with a maternally derived OG2 allele (OG2 mat /-) express GFP in the oocyte and during preimplantation development until the blastocyst stage indicating a maternal and embryonic expression pattern. F1-embryos with a paternally inherited OG2 allele (OG2 pat /-) express GFP from the 4- to 8-cell stage onwards showing only embryonic expression. This allows to study allele specific knock down of GFP expression. RNA interference (RNAi) was highly efficient in embryos with the paternally inherited GFP allele, whereas embryos with the maternally inherited GFP allele showed a delayed and less stringent suppression, indicating that the initial levels of the target transcript and the half life of the protein affect RNAi efficacy. RT-PCR analysis revealed only minimum of GFP mRNA. These results have implications for studies of gene silencing in mammalian embryos

  6. Angiomodulin is a specific marker of vasculature and regulates VEGF-A dependent neo-angiogenesis

    Science.gov (United States)

    Hooper, Andrea T.; Shmelkov, Sergey V.; Gupta, Sunny; Milde, Till; Bambino, Kathryn; Gillen, Kelly; Goetz, Mollie; Chavala, Sai; Baljevic, Muhamed; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; Vahdat, Linda; Evans, Todd; Rafii, Shahin

    2010-01-01

    Blood vessel formation is controlled by the balance between pro- and anti-angiogenic pathways. Although much is known about the factors that drive sprouting of neovessels, the factors that stabilize and pattern neovessels are undefined. The expression of angiomodulin (AGM), a VEGF-A binding protein, was increased in the vasculature of several human tumors as compared to normal tissue, raising the hypothesis that AGM may modulate VEGF-A-dependent vascular patterning. To elucidate the expression pattern of AGM, we developed an AGM knockin reporter mouse (AGMlacZ/+) wherein we demonstrate that AGM is predominantly expressed in the vasculature of developing embryos and adult organs. During physiological and pathological angiogenesis, AGM is upregulated in the angiogenic vasculature. Using the zebrafish model, we found that AGM is restricted to developing vasculature by 17-22 hpf. Blockade of AGM activity with morpholino oligomers (MO) results in prominent angiogenesis defects in vascular sprouting and remodeling. Concurrent knockdown of both AGM and VEGF-A results in synergistic angiogenesis defects. When VEGF-A is overexpressed, the compensatory induction of the VEGF-A receptor, VEGFR-2/flk-1, is blocked by the simultaneous injection of AGM MO. These results demonstrate that the vascular-specific marker AGM modulates vascular remodeling in part by temporizing the pro-angiogenic effects of VEGF-A. PMID:19542015

  7. Intra-individual gait pattern variability in specific situations: Implications for forensic gait analysis.

    Science.gov (United States)

    Ludwig, Oliver; Dillinger, Steffen; Marschall, Franz

    2016-07-01

    In this study, inter- and intra-individual gait pattern differences are examined in various gait situations by means of phase diagrams of the extremity angles (cyclograms). 8 test subjects walked along a walking distance of 6m under different conditions three times each: barefoot, wearing sneakers, wearing combat boots, after muscular fatigue, and wearing a full-face motorcycle helmet restricting vision. The joint angles of foot, knee, and hip were recorded in the sagittal plane. The coupling of movements was represented by time-adjusted cyclograms, and the inter- and intra-individual differences were captured by calculating the similarity between different gait patterns. Gait pattern variability was often greater between the defined test situations than between the individual test subjects. The results have been interpreted considering neurophysiological regulation mechanisms. Footwear, masking, and fatigue were interpreted as disturbance parameters, each being a cause for gait pattern variability and complicating the inference of identity of persons in video recordings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Patterns and processes of habitat-specific demographic variability in exploited marine species

    NARCIS (Netherlands)

    Vasconcelos, R.P.; Eggleston, D.B.; Pape, le O.; Tulp, I.Y.M.

    2014-01-01

    Population dynamics are governed by four demographic rates: births, deaths, immigration, and emigration. Variation in these rates and processes underlying such variation can be used to prioritize habitat conservation and restoration as well as to parameterize models that predict habitat-specific

  9. Saddlepoint expansions for sums of Markov dependent variables on a continuous state space

    DEFF Research Database (Denmark)

    Jensen, J.L.

    1991-01-01

    Based on the conjugate kernel studied in Iscoe et al. (1985) we derive saddlepoint expansions for either the density or distribution function of a sum f(X1)+...+f(Xn), where the Xi's constitute a Markov chain. The chain is assumed to satisfy a strong recurrence condition which makes the results...... here very similar to the classical results for i.i.d. variables. In particular we establish also conditions under which the expansions hold uniformly over the range of the saddlepoint. Expansions are also derived for sums of the form f(X1, X0)+f(X2, X1)+...+f(Xn, Xn-1) although the uniformity result...

  10. Interindividual variability in the dose-specific effect of dopamine on carotid chemoreceptor sensitivity to hypoxia

    Science.gov (United States)

    Limberg, Jacqueline K.; Johnson, Blair D.; Holbein, Walter W.; Ranadive, Sushant M.; Mozer, Michael T.

    2015-01-01

    Human studies use varying levels of low-dose (1-4 μg·kg−1·min−1) dopamine to examine peripheral chemosensitivity, based on its known ability to blunt carotid body responsiveness to hypoxia. However, the effect of dopamine on the ventilatory responses to hypoxia is highly variable between individuals. Thus we sought to determine 1) the dose response relationship between dopamine and peripheral chemosensitivity as assessed by the ventilatory response to hypoxia in a cohort of healthy adults, and 2) potential confounding cardiovascular responses at variable low doses of dopamine. Young, healthy adults (n = 30, age = 32 ± 1, 24 male/6 female) were given intravenous (iv) saline and a range of iv dopamine doses (1–4 μg·kg−1·min−1) prior to and throughout five hypoxic ventilatory response (HVR) tests. Subjects initially received iv saline, and after each HVR the dopamine infusion rate was increased by 1 μg·kg−1·min−1. Tidal volume, respiratory rate, heart rate, blood pressure, and oxygen saturation were continuously measured. Dopamine significantly reduced HVR at all doses (P HVR in the high group only (P HVR in the low group (P > 0.05). Dopamine infusion also resulted in a reduction in blood pressure (3 μg·kg−1·min−1) and total peripheral resistance (1–4 μg·kg−1·min−1), driven primarily by subjects with low baseline chemosensitivity. In conclusion, we did not find a single dose of dopamine that elicited a nadir HVR in all subjects. Additionally, potential confounding cardiovascular responses occur with dopamine infusion, which may limit its usage. PMID:26586909

  11. Interindividual variability in the dose-specific effect of dopamine on carotid chemoreceptor sensitivity to hypoxia.

    Science.gov (United States)

    Limberg, Jacqueline K; Johnson, Blair D; Holbein, Walter W; Ranadive, Sushant M; Mozer, Michael T; Joyner, Michael J

    2016-01-15

    Human studies use varying levels of low-dose (1-4 μg·kg(-1)·min(-1)) dopamine to examine peripheral chemosensitivity, based on its known ability to blunt carotid body responsiveness to hypoxia. However, the effect of dopamine on the ventilatory responses to hypoxia is highly variable between individuals. Thus we sought to determine 1) the dose response relationship between dopamine and peripheral chemosensitivity as assessed by the ventilatory response to hypoxia in a cohort of healthy adults, and 2) potential confounding cardiovascular responses at variable low doses of dopamine. Young, healthy adults (n = 30, age = 32 ± 1, 24 male/6 female) were given intravenous (iv) saline and a range of iv dopamine doses (1-4 μg·kg(-1)·min(-1)) prior to and throughout five hypoxic ventilatory response (HVR) tests. Subjects initially received iv saline, and after each HVR the dopamine infusion rate was increased by 1 μg·kg(-1)·min(-1). Tidal volume, respiratory rate, heart rate, blood pressure, and oxygen saturation were continuously measured. Dopamine significantly reduced HVR at all doses (P HVR in the high group only (P HVR in the low group (P > 0.05). Dopamine infusion also resulted in a reduction in blood pressure (3 μg·kg(-1)·min(-1)) and total peripheral resistance (1-4 μg·kg(-1)·min(-1)), driven primarily by subjects with low baseline chemosensitivity. In conclusion, we did not find a single dose of dopamine that elicited a nadir HVR in all subjects. Additionally, potential confounding cardiovascular responses occur with dopamine infusion, which may limit its usage. Copyright © 2016 the American Physiological Society.

  12. Polymer-Mediated Delivery of siRNAs to Hepatocellular Carcinoma: Variables Affecting Specificity and Effectiveness

    Directory of Open Access Journals (Sweden)

    Rossella Farra

    2018-03-01

    Full Text Available Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD and particularly small interfering RNAs (siRNAs, are attractive molecules due to the possibility to be engineered to target specific tumor genes. On the other hand, polymeric-based delivery systems are emerging as versatile carriers to generate tumor-targeted delivery systems. Here we will focus on the most recent findings in the selection of siRNA/polymeric targeted delivery systems for hepatocellular carcinoma (HCC, a human tumor for which currently available therapeutic approaches are poorly effective. In addition, we will discuss the most attracting and, in our opinion, promising siRNA-polymer combinations for HCC in relation to the biological features of HCC tissue. Attention will be also put on the mathematical description of the mechanisms ruling siRNA-carrier delivery, this being an important aspect to improve effectiveness reducing the experimental work.

  13. A hypoxia- and {alpha}-fetoprotein-dependent oncolytic adenovirus exhibits specific killing of hepatocellular carcinomas.

    Science.gov (United States)

    Kwon, Oh-Joon; Kim, Pyung-Hwan; Huyn, Steven; Wu, Lily; Kim, Minjung; Yun, Chae-Ok

    2010-12-15

    Oncolytic adenoviruses (Ad) constitute a new promising modality of cancer gene therapy that displays improved efficacy over nonreplicating Ads. We have previously shown that an E1B 19-kDa-deleted oncolytic Ad exhibits a strong cell-killing effect but lacks tumor selectivity. To achieve hepatoma-restricted cytotoxicity and enhance replication of Ad within the context of tumor microenvironment, we used a modified human α-fetoprotein (hAFP) promoter to control the replication of Ad with a hypoxia response element (HRE). We constructed Ad-HRE(6)/hAFPΔ19 and Ad-HRE(12)/hAFPΔ19 that incorporated either 6 or 12 copies of HRE upstream of promoter. The promoter activity and specificity to hepatoma were examined by luciferase assay and fluorescence-activated cell sorting analysis. In addition, the AFP expression- and hypoxia-dependent in vitro cytotoxicity of Ad-HRE(6)/hAFPΔ19 and Ad-HRE(12)/hAFPΔ19 was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cytopathic effect assay. In vivo tumoricidal activity on subcutaneous and liver orthotopic model was monitored by noninvasive molecular imaging. Ad-HRE(12)/hAFPΔ19 exhibited enhanced tumor selectivity and cell-killing activity when compared with Ad-hAFPΔ19. The tumoricidal activity of Ad-HRE(12)/hAFPΔ19 resulted in significant inhibition of tumor growth in both subcutaneous and orthotopic models. Histologic examination of the primary tumor after treatment confirmed accumulation of viral particles near hypoxic areas. Furthermore, Ad-HRE(12)/hAFPΔ19 did not cause severe inflammatory immune response and toxicity after systemic injection. The results presented here show the advantages of incorporating HREs into a hAFP promoter-driven oncolytic virus. This system is unique in that it acts in both a tissue-specific and tumor environment-selective manner. The greatly enhanced selectivity and tumoricidal activity of Ad-HRE(12)/hAFPΔ19 make it a promising therapeutic agent in the treatment

  14. Dimethylfumarate attenuates restenosis after acute vascular injury by cell-specific and Nrf2-dependent mechanisms

    Directory of Open Access Journals (Sweden)

    Chang Joo Oh

    2014-01-01

    Full Text Available Excessive proliferation of vascular smooth muscle cells (VSMCs and incomplete re-endothelialization is a major clinical problem limiting the long-term efficacy of percutaneous coronary angioplasty. We tested if dimethylfumarate (DMF, an anti-psoriasis drug, could inhibit abnormal vascular remodeling via NF−E2-related factor 2 (Nrf2-NAD(PH quinone oxidoreductase 1 (NQO1 activity. DMF significantly attenuated neointimal hyperplasia induced by balloon injury in rat carotid arteries via suppression of the G1 to S phase transition resulting from induction of p21 protein in VSMCs. Initially, DMF increased p21 protein stability through an enhancement in Nrf2 activity without an increase in p21 mRNA. Later on, DMF stimulated p21 mRNA expression through a process dependent on p53 activity. However, heme oxygenase-1 (HO-1 or NQO1 activity, well-known target genes induced by Nrf2, were dispensable for the DMF induction of p21 protein and the effect on the VSMC proliferation. Likewise, DMF protected endothelial cells from TNF-α-induced apoptosis and the dysfunction characterized by decreased eNOS expression. With knock-down of Nrf2 or NQO1, DMF failed to prevent TNF-α-induced cell apoptosis and decreased eNOS expression. Also, CD31 expression, an endothelial specific marker, was restored in vivo by DMF. In conclusion, DMF prevented abnormal proliferation in VSMCs by G1 cell cycle arrest via p21 upregulation driven by Nrf2 and p53 activity, and had a beneficial effect on TNF-α-induced apoptosis and dysfunction in endothelial cells through Nrf2–NQO1 activity suggesting that DMF might be a therapeutic drug for patients with vascular disease.

  15. SNOSite: exploiting maximal dependence decomposition to identify cysteine S-nitrosylation with substrate site specificity.

    Directory of Open Access Journals (Sweden)

    Tzong-Yi Lee

    Full Text Available S-nitrosylation, the covalent attachment of a nitric oxide to (NO the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-nitrosylation remains unknown. Based on a total of 586 experimentally identified S-nitrosylation sites from SNAP/L-cysteine-stimulated mouse endothelial cells, this work presents an informatics investigation on S-nitrosylation sites including structural factors such as the flanking amino acids composition, the accessible surface area (ASA and physicochemical properties, i.e. positive charge and side chain interaction parameter. Due to the difficulty to obtain the conserved motifs by conventional motif analysis, maximal dependence decomposition (MDD has been applied to obtain statistically significant conserved motifs. Support vector machine (SVM is applied to generate predictive model for each MDD-clustered motif. According to five-fold cross-validation, the MDD-clustered SVMs could achieve an accuracy of 0.902, and provides a promising performance in an independent test set. The effectiveness of the model was demonstrated on the correct identification of previously reported S-nitrosylation sites of Bos taurus dimethylarginine dimethylaminohydrolase 1 (DDAH1 and human hemoglobin subunit beta (HBB. Finally, the MDD-clustered model was adopted to construct an effective web-based tool, named SNOSite (http://csb.cse.yzu.edu.tw/SNOSite/, for identifying S-nitrosylation sites on the uncharacterized protein sequences.

  16. Fruit specific variability in capsaicinoid accumulation and transcription of structural and regulatory genes in Capsicum fruit.

    Science.gov (United States)

    Keyhaninejad, Neda; Curry, Jeanne; Romero, Joslynn; O'Connell, Mary A

    2014-02-01

    Accumulation of capsaicinoids in the placental tissue of ripening chile (Capsicum spp.) fruit follows the coordinated expression of multiple biosynthetic enzymes producing the substrates for capsaicin synthase. Transcription factors are likely agents to regulate expression of these biosynthetic genes. Placental RNAs from habanero fruit (Capsicum chinense) were screened for expression of candidate transcription factors; with two candidate genes identified, both in the ERF family of transcription factors. Characterization of these transcription factors, Erf and Jerf, in nine chile cultivars with distinct capsaicinoid contents demonstrated a correlation of expression with pungency. Amino acid variants were observed in both ERF and JERF from different chile cultivars; none of these changes involved the DNA binding domains. Little to no transcription of Erf was detected in non-pungent Capsium annuum or C. chinense mutants. This correlation was characterized at an individual fruit level in a set of jalapeño (C. annuum) lines again with distinct and variable capsaicinoid contents. Both Erf and Jerf are expressed early in fruit development, 16-20 days post-anthesis, at times prior to the accumulation of capsaicinoids in the placental tissues. These data support the hypothesis that these two members of the complex ERF family participate in regulation of the pungency phenotype in chile. Copyright © 2013. Published by Elsevier Ireland Ltd.

  17. ENERGY-DEPENDENT POWER SPECTRAL STATES AND ORIGIN OF APERIODIC VARIABILITY IN BLACK HOLE BINARIES

    International Nuclear Information System (INIS)

    Yu Wenfei; Zhang Wenda

    2013-01-01

    We found that the black hole candidate MAXI J1659–152 showed distinct power spectra, i.e., power-law noise (PLN) versus band-limited noise (BLN) plus quasi-periodic oscillations (QPOs) below and above about 2 keV, respectively, in observations with Swift and the Rossi X-ray Timing Explorer during the 2010 outburst, indicating a high energy cutoff of the PLN and a low energy cutoff of the BLN and QPOs around 2 keV. The emergence of the PLN and the fading of the BLN and QPOs initially took place below 2 keV when the source entered the hard intermediate state and settled in the soft state three weeks later. The evolution was accompanied by the emergence of the disk spectral component and decreases in the amplitudes of variability in the soft and hard X-ray bands. Our results indicate that the PLN is associated with an optically thick disk in both hard and intermediate states, and the power spectral state is independent of the X-ray energy spectral state in a broadband view. We suggest that in the hard or intermediate state, the BLN and QPOs emerge from the innermost hot flow subjected to Comptonization, while the PLN originates from the optically thick disk farther out. The energy cutoffs of the PLN and the BLN or QPOs then follow the temperature of the seed photons from the inner edge of the optically thick disk, while the high frequency cutoff of the PLN follows the orbital frequency of the inner edge of the optically thick disk as well.

  18. Temperature-dependent daily variability of precipitable water in special sensor microwave/imager observations

    Science.gov (United States)

    Gutowski, William J.; Lindemulder, Elizabeth A.; Jovaag, Kari

    1995-01-01

    We use retrievals of atmospheric precipitable water from satellite microwave observations and analyses of near-surface temperature to examine the relationship between these two fields on daily and longer time scales. The retrieval technique producing the data used here is most effective over the open ocean, so the analysis focuses on the southern hemisphere's extratropics, which have an extensive ocean surface. For both the total and the eddy precipitable water fields, there is a close correspondence between local variations in the precipitable water and near-surface temperature. The correspondence appears particularly strong for synoptic and planetary scale transient eddies. More specifically, the results support a typical modeling assumption that transient eddy moisture fields are proportional to transient eddy temperature fields under the assumption f constant relative humidity.

  19. Dark focus of accommodation as dependent and independent variables in visual display technology

    Science.gov (United States)

    Jones, Sherrie; Kennedy, Robert; Harm, Deborah

    1992-01-01

    When independent stimuli are available for accommodation, as in the dark or under low contrast conditions, the lens seeks its resting position. Individual differences in resting positions are reliable, under autonomic control, and can change with visual task demands. We hypothesized that motion sickness in a flight simulator might result in dark focus changes. Method: Subjects received training flights in three different Navy flight simulators. Two were helicopter simulators entailed CRT presentation using infinity optics, one involved a dome presentation of a computer graphic visual projection system. Results: In all three experiments there were significant differences between dark focus activity before and after simulator exposure when comparisons were made between sick and not-sick pilot subjects. In two of these experiments, the average shift in dark focus for the sick subjects was toward increased myopia when each subject was compared to his own baseline. In the third experiment, the group showed an average shift outward of small amount and the subjects who were sick showed significantly less outward movement than those who were symptom free. Conclusions: Although the relationship is not a simple one, dark focus changes in simulator sickness imply parasympathetic activity. Because changes can occur in relation to endogenous and exogenous events, such measurement may have useful applications as dependent measures in studies of visually coupled systems, virtual reality systems, and space adaptation syndrome.

  20. Modeling Time-Dependent Behavior of Concrete Affected by Alkali Silica Reaction in Variable Environmental Conditions.

    Science.gov (United States)

    Alnaggar, Mohammed; Di Luzio, Giovanni; Cusatis, Gianluca

    2017-04-28

    Alkali Silica Reaction (ASR) is known to be a serious problem for concrete worldwide, especially in high humidity and high temperature regions. ASR is a slow process that develops over years to decades and it is influenced by changes in environmental and loading conditions of the structure. The problem becomes even more complicated if one recognizes that other phenomena like creep and shrinkage are coupled with ASR. This results in synergistic mechanisms that can not be easily understood without a comprehensive computational model. In this paper, coupling between creep, shrinkage and ASR is modeled within the Lattice Discrete Particle Model (LDPM) framework. In order to achieve this, a multi-physics formulation is used to compute the evolution of temperature, humidity, cement hydration, and ASR in both space and time, which is then used within physics-based formulations of cracking, creep and shrinkage. The overall model is calibrated and validated on the basis of experimental data available in the literature. Results show that even during free expansions (zero macroscopic stress), a significant degree of coupling exists because ASR induced expansions are relaxed by meso-scale creep driven by self-equilibriated stresses at the meso-scale. This explains and highlights the importance of considering ASR and other time dependent aging and deterioration phenomena at an appropriate length scale in coupled modeling approaches.

  1. Single genome retrieval of context-dependent variability in mutation rates for human germline.

    Science.gov (United States)

    Sahakyan, Aleksandr B; Balasubramanian, Shankar

    2017-01-13

    Accurate knowledge of the core components of substitution rates is of vital importance to understand genome evolution and dynamics. By performing a single-genome and direct analysis of 39,894 retrotransposon remnants, we reveal sequence context-dependent germline nucleotide substitution rates for the human genome. The rates are characterised through rate constants in a time-domain, and are made available through a dedicated program (Trek) and a stand-alone database. Due to the nature of the method design and the imposed stringency criteria, we expect our rate constants to be good estimates for the rates of spontaneous mutations. Benefiting from such data, we study the short-range nucleotide (up to 7-mer) organisation and the germline basal substitution propensity (BSP) profile of the human genome; characterise novel, CpG-independent, substitution prone and resistant motifs; confirm a decreased tendency of moieties with low BSP to undergo somatic mutations in a number of cancer types; and, produce a Trek-based estimate of the overall mutation rate in human. The extended set of rate constants we report may enrich our resources and help advance our understanding of genome dynamics and evolution, with possible implications for the role of spontaneous mutations in the emergence of pathological genotypes and neutral evolution of proteomes.

  2. Spatio-temporal dependencies between hospital beds, physicians and health expenditure using visual variables and data classification in statistical table

    Science.gov (United States)

    Medyńska-Gulij, Beata; Cybulski, Paweł

    2016-06-01

    This paper analyses the use of table visual variables of statistical data of hospital beds as an important tool for revealing spatio-temporal dependencies. It is argued that some of conclusions from the data about public health and public expenditure on health have a spatio-temporal reference. Different from previous studies, this article adopts combination of cartographic pragmatics and spatial visualization with previous conclusions made in public health literature. While the significant conclusions about health care and economic factors has been highlighted in research papers, this article is the first to apply visual analysis to statistical table together with maps which is called previsualisation.

  3. Spatio-temporal dependencies between hospital beds, physicians and health expenditure using visual variables and data classification in statistical table

    Directory of Open Access Journals (Sweden)

    Medyńska-Gulij Beata

    2016-06-01

    Full Text Available This paper analyses the use of table visual variables of statistical data of hospital beds as an important tool for revealing spatio-temporal dependencies. It is argued that some of conclusions from the data about public health and public expenditure on health have a spatio-temporal reference. Different from previous studies, this article adopts combination of cartographic pragmatics and spatial visualization with previous conclusions made in public health literature. While the significant conclusions about health care and economic factors has been highlighted in research papers, this article is the first to apply visual analysis to statistical table together with maps which is called previsualisation.

  4. Economics of site-specific and variable-dose herbicide application

    DEFF Research Database (Denmark)

    Ørum, Jens Erik; Kudsk, Per; Jensen, Peter Kryger

    2017-01-01

    Site-specific application of pesticides has so far focused mainly on herbicides. The purpose of precision farming technologies in relation to herbicide use is to reduce herbicide cost and environmental impact from spraying, but at the same time to achieve acceptable weed control. Another purpose...... is to increase the spraying capacity, to reduce the number of sprayer refills, and finally to minimize time spent on weed monitoring. In this chapter the relevance and profitability of four precision herbicide application technologies, two weed detection technologies and a low dose decision support system (DSS......) is analysed. With a low dose herbicide, cost can be reduced by 20–50%. It requires, however, proper monitoring of weeds, which can be a time-consuming task that again requires that the farmer is able to identify the dominant weed species. The current development of high-speed camera and software systems can...

  5. The Dependencies of Ecosystem Pattern, Structure, and Dynamics on Climate, Climate Variability, and Climate Change

    Science.gov (United States)

    Flanagan, S.; Hurtt, G. C.; Fisk, J. P.; Rourke, O.

    2012-12-01

    A robust understanding of the sensitivity of the pattern, structure, and dynamics of ecosystems to climate, climate variability, and climate change is needed to predict ecosystem responses to current and projected climate change. We present results of a study designed to first quantify the sensitivity of ecosystems to climate through the use of climate and ecosystem data, and then use the results to test the sensitivity of the climate data in a state-of the art ecosystem model. A database of available ecosystem characteristics such as mean canopy height, above ground biomass, and basal area was constructed from sources like the National Biomass and Carbon Dataset (NBCD). The ecosystem characteristics were then paired by latitude and longitude with the corresponding climate characteristics temperature, precipitation, photosynthetically active radiation (PAR) and dew point that were retrieved from the North American Regional Reanalysis (NARR). The average yearly and seasonal means of the climate data, and their associated maximum and minimum values, over the 1979-2010 time frame provided by NARR were constructed and paired with the ecosystem data. The compiled results provide natural patterns of vegetation structure and distribution with regard to climate data. An advanced ecosystem model, the Ecosystem Demography model (ED), was then modified to allow yearly alterations to its mechanistic climate lookup table and used to predict the sensitivities of ecosystem pattern, structure, and dynamics to climate data. The combined ecosystem structure and climate data results were compared to ED's output to check the validity of the model. After verification, climate change scenarios such as those used in the last IPCC were run and future forest structure changes due to climate sensitivities were identified. The results of this study can be used to both quantify and test key relationships for next generation models. The sensitivity of ecosystem characteristics to climate data

  6. Error Processing and Gender-Shared and -Specific Neural Predictors of Relapse in Cocaine Dependence

    Science.gov (United States)

    Luo, Xi; Zhang, Sheng; Hu, Sien; Bednarski, Sarah R.; Erdman, Emily; Farr, Olivia M.; Hong, Kwang-Ik; Sinha, Rajita; Mazure, Carolyn M.; Li, Chiang-shan R.

    2013-01-01

    Deficits in cognitive control are implicated in cocaine dependence. Previously, combining functional magnetic resonance imaging and a stop signal task, we demonstrated altered cognitive control in cocaine-dependent individuals. However, the clinical implications of these cross-sectional findings and, in particular, whether the changes were…

  7. Massively parallel amplicon sequencing reveals isotype-specific variability of antimicrobial peptide transcripts in Mytilus galloprovincialis.

    Directory of Open Access Journals (Sweden)

    Umberto Rosani

    Full Text Available BACKGROUND: Effective innate responses against potential pathogens are essential in the living world and possibly contributed to the evolutionary success of invertebrates. Taken together, antimicrobial peptide (AMP precursors of defensin, mytilin, myticin and mytimycin can represent about 40% of the hemocyte transcriptome in mussels injected with viral-like and bacterial preparations, and unique profiles of myticin C variants are expressed in single mussels. Based on amplicon pyrosequencing, we have ascertained and compared the natural and Vibrio-induced diversity of AMP transcripts in mussel hemocytes from three European regions. METHODOLOGY/PRINCIPAL FINDINGS: Hemolymph was collected from mussels farmed in the coastal regions of Palavas (France, Vigo (Spain and Venice (Italy. To represent the AMP families known in M. galloprovincialis, nine transcript sequences have been selected, amplified from hemocyte RNA and subjected to pyrosequencing. Hemolymph from farmed (offshore and wild (lagoon Venice mussels, both injected with 10(7 Vibrio cells, were similarly processed. Amplicon pyrosequencing emphasized the AMP transcript diversity, with Single Nucleotide Changes (SNC minimal for mytilin B/C and maximal for arthropod-like defensin and myticin C. Ratio of non-synonymous vs. synonymous changes also greatly differed between AMP isotypes. Overall, each amplicon revealed similar levels of nucleotidic variation across geographical regions, with two main sequence patterns confirmed for mytimycin and no substantial changes after immunostimulation. CONCLUSIONS/SIGNIFICANCE: Barcoding and bidirectional pyrosequencing allowed us to map and compare the transcript diversity of known mussel AMPs. Though most of the genuine cds variation was common to the analyzed samples we could estimate from 9 to 106 peptide variants in hemolymph pools representing 100 mussels, depending on the AMP isoform and sampling site. In this study, no prevailing SNC patterns related

  8. Nor-ursodeoxycholic acid reverses hepatocyte-specific nemo-dependent steatohepatitis.

    Science.gov (United States)

    Beraza, Naiara; Ofner-Ziegenfuss, Lisa; Ehedego, Haksier; Boekschoten, Mark; Bischoff, Stephan C; Mueller, Michael; Trauner, Michael; Trautwein, Christian

    2011-03-01

    Hepatocyte-specific NEMO/NF-κB deleted mice (NEMO(Δhepa)) develop spontaneous non-alcoholic steatohepatitis (NASH). Free fatty acids and bile acids promote DR5 expression. TRAIL/NK cell-mediated activation of TRAIL-R2/DR5 plays an important role during acute injury in NEMO(Δhepa) mice. To inhibit the progression of NASH in the absence of hepatocyte-NEMO/NF-kB signaling. NEMOf/f and NEMO(Δhepa) mice were fed with a low-fat diet, and with two anticholestatic diets; UDCA and NorUDCA. The impact of these treatments on the progression of NASH was evaluated. We show that high expression of DR5 in livers from NEMO(Δhepa) mice is accompanied by an abundant presence of bile acids (BAs), misregulation of BA transporters and significant alteration of lipid metabolism-related genes. Additionally, mice lacking NEMO in hepatocytes spontaneously showed ductular response at young age. Unexpectedly, feeding of NEMO(Δhepa) mice with low-fat diet failed to improve chronic liver injury. Conversely, anti-cholestatic treatment with nor-ursodeoxycholic acid (NorUDCA), but not with ursodeoxycholic acid (UDCA), led to a significant attenuation of liver damage in NEMO(Δhepa) mice. The strong therapeutic effect of NorUDCA relied on a significant downregulation of LXR-dependent lipogenesis and the normalisation of BA metabolism through mechanisms involving cross-talk between Cyp7a1 and SHP. This was associated with the significant improvement of liver histology, NEMO(Δhepa)/NorUDCA-treated mice showed lower apoptosis and reduced CyclinD1 expression, indicating attenuation of the compensatory proliferative response to hepatocellular damage. Finally, fibrosis and ductular reaction markers were significantly reduced in NorUDCA-treated NEMO(Δhepa) mice. Overall, our work demonstrates the contribution of bile acids metabolism to the progression of NASH in the absence of hepatocyte-NF-kB through mechanisms involving DR5-apoptosis, inflammation and fibrosis. Our work suggests a potential

  9. Insulin-dependent glucose metabolism in dairy cows with variable fat mobilization around calving.

    Science.gov (United States)

    Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Görs, S; Röntgen, M; Sauerwein, H; Bruckmaier, R M; Metges, C C; Kuhla, B; Hammon, H M

    2016-08-01

    clamps, pp nonesterified fatty acid concentrations did not reach the ap levels. The study demonstrated a minor influence of different degrees of body fat mobilization on insulin metabolism in cows during the transition period. The distinct decrease in the glucose-dependent release of insulin pp is the most striking finding that explains the impaired insulin action after calving, but does not explain differences in body fat mobilization between HLFC and LLFC cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. Temperature and air-fuel ratio dependent specific heat ratio functions for lean burned and unburned mixture

    International Nuclear Information System (INIS)

    Ceviz, M.A.; Kaymaz, I.

    2005-01-01

    The most important thermodynamic property used in heat release calculations for engines is the specific heat ratio. The functions proposed in the literature for the specific heat ratio are temperature dependent and apply at or near stoichiometric air-fuel ratios. However, the specific heat ratio is also influenced by the gas composition in the engine cylinder and especially becomes important for lean combustion engines. In this study, temperature and air-fuel ratio dependent specific heat ratio functions were derived to minimize the error by using an equilibrium combustion model for burned and unburned mixtures separately. After the error analysis between the equilibrium combustion model and the derived functions is presented, the results of the global specific heat ratio function, as varying with mass fraction burned, were compared with the proposed functions in the literature. The results of the study showed that the derived functions are more feasible at lean operating conditions of a spark ignition engine

  11. Variability among the Most Rapidly Evolving Plastid Genomic Regions is Lineage-Specific: Implications of Pairwise Genome Comparisons in Pyrus (Rosaceae) and Other Angiosperms for Marker Choice

    Science.gov (United States)

    Ter-Voskanyan, Hasmik; Allgaier, Martin; Borsch, Thomas

    2014-01-01

    Plastid genomes exhibit different levels of variability in their sequences, depending on the respective kinds of genomic regions. Genes are usually more conserved while noncoding introns and spacers evolve at a faster pace. While a set of about thirty maximum variable noncoding genomic regions has been suggested to provide universally promising phylogenetic markers throughout angiosperms, applications often require several regions to be sequenced for many individuals. Our project aims to illuminate evolutionary relationships and species-limits in the genus Pyrus (Rosaceae)—a typical case with very low genetic distances between taxa. In this study, we have sequenced the plastid genome of Pyrus spinosa and aligned it to the already available P. pyrifolia sequence. The overall p-distance of the two Pyrus genomes was 0.00145. The intergenic spacers between ndhC–trnV, trnR–atpA, ndhF–rpl32, psbM–trnD, and trnQ–rps16 were the most variable regions, also comprising the highest total numbers of substitutions, indels and inversions (potentially informative characters). Our comparative analysis of further plastid genome pairs with similar low p-distances from Oenothera (representing another rosid), Olea (asterids) and Cymbidium (monocots) showed in each case a different ranking of genomic regions in terms of variability and potentially informative characters. Only two intergenic spacers (ndhF–rpl32 and trnK–rps16) were consistently found among the 30 top-ranked regions. We have mapped the occurrence of substitutions and microstructural mutations in the four genome pairs. High AT content in specific sequence elements seems to foster frequent mutations. We conclude that the variability among the fastest evolving plastid genomic regions is lineage-specific and thus cannot be precisely predicted across angiosperms. The often lineage-specific occurrence of stem-loop elements in the sequences of introns and spacers also governs lineage-specific mutations

  12. Variability among the most rapidly evolving plastid genomic regions is lineage-specific: implications of pairwise genome comparisons in Pyrus (Rosaceae and other angiosperms for marker choice.

    Directory of Open Access Journals (Sweden)

    Nadja Korotkova

    Full Text Available Plastid genomes exhibit different levels of variability in their sequences, depending on the respective kinds of genomic regions. Genes are usually more conserved while noncoding introns and spacers evolve at a faster pace. While a set of about thirty maximum variable noncoding genomic regions has been suggested to provide universally promising phylogenetic markers throughout angiosperms, applications often require several regions to be sequenced for many individuals. Our project aims to illuminate evolutionary relationships and species-limits in the genus Pyrus (Rosaceae-a typical case with very low genetic distances between taxa. In this study, we have sequenced the plastid genome of Pyrus spinosa and aligned it to the already available P. pyrifolia sequence. The overall p-distance of the two Pyrus genomes was 0.00145. The intergenic spacers between ndhC-trnV, trnR-atpA, ndhF-rpl32, psbM-trnD, and trnQ-rps16 were the most variable regions, also comprising the highest total numbers of substitutions, indels and inversions (potentially informative characters. Our comparative analysis of further plastid genome pairs with similar low p-distances from Oenothera (representing another rosid, Olea (asterids and Cymbidium (monocots showed in each case a different ranking of genomic regions in terms of variability and potentially informative characters. Only two intergenic spacers (ndhF-rpl32 and trnK-rps16 were consistently found among the 30 top-ranked regions. We have mapped the occurrence of substitutions and microstructural mutations in the four genome pairs. High AT content in specific sequence elements seems to foster frequent mutations. We conclude that the variability among the fastest evolving plastid genomic regions is lineage-specific and thus cannot be precisely predicted across angiosperms. The often lineage-specific occurrence of stem-loop elements in the sequences of introns and spacers also governs lineage-specific mutations. Sequencing

  13. Colony-specific investigations reveal highly variable responses among individual corals to ocean acidification and warming.

    Science.gov (United States)

    Kavousi, Javid; Reimer, James Davis; Tanaka, Yasuaki; Nakamura, Takashi

    2015-08-01

    As anthropogenic climate change is an ongoing concern, scientific investigations on its impacts on coral reefs are increasing. Although impacts of combined ocean acidification (OA) and temperature stress (T) on reef-building scleractinian corals have been studied at the genus, species and population levels, there are little data available on how individual corals respond to combined OA and anomalous temperatures. In this study, we exposed individual colonies of Acropora digitifera, Montipora digitata and Porites cylindrica to four pCO2-temperature treatments including 400 μatm-28 °C, 400 μatm-31 °C, 1000 μatm-28 °C and 1000 μatm-31 °C for 26 days. Physiological parameters including calcification, protein content, maximum photosynthetic efficiency, Symbiodinium density, and chlorophyll content along with Symbiodinium type of each colony were examined. Along with intercolonial responses, responses of individual colonies versus pooled data to the treatments were investigated. The main results were: 1) responses to either OA or T or their combination were different between individual colonies when considering physiological functions; 2) tolerance to either OA or T was not synonymous with tolerance to the other parameter; 3) tolerance to both OA and T did not necessarily lead to tolerance of OA and T combined (OAT) at the same time; 4) OAT had negative, positive or no impacts on physiological functions of coral colonies; and 5) pooled data were not representative of responses of all individual colonies. Indeed, the pooled data obscured actual responses of individual colonies or presented a response that was not observed in any individual. From the results of this study we recommend improving experimental designs of studies investigating physiological responses of corals to climate change by complementing them with colony-specific examinations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence.

    Science.gov (United States)

    Kendler, Kenneth S; Myers, John; Prescott, Carol A

    2007-11-01

    Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. Lifetime history by structured clinical interview. General community. Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence

  15. Variable Domain N-Linked Glycans Acquired During Antigen-Specific Immune Responses Can Contribute to Immunoglobulin G Antibody Stability

    Directory of Open Access Journals (Sweden)

    Fleur S. van de Bovenkamp

    2018-04-01

    Full Text Available Immunoglobulin G (IgG can contain N-linked glycans in the variable domains, the so-called Fab glycans, in addition to the Fc glycans in the CH2 domains. These Fab glycans are acquired following introduction of N-glycosylation sites during somatic hypermutation and contribute to antibody diversification. We investigated whether Fab glycans may—in addition to affecting antigen binding—contribute to antibody stability. By analyzing thermal unfolding profiles of antibodies with or without Fab glycans, we demonstrate that introduction of Fab glycans can improve antibody stability. Strikingly, removal of Fab glycans naturally acquired during antigen-specific immune responses can deteriorate antibody stability, suggesting in vivo selection of stable, glycosylated antibodies. Collectively, our data show that variable domain N-linked glycans acquired during somatic hypermutation can contribute to IgG antibody stability. These findings indicate that introducing Fab glycans may represent a mechanism to improve therapeutic/diagnostic antibody stability.

  16. Variability in colonization of arbuscular mycorrhizal fungi and its effect on mycorrhizal dependency of improved and unimproved soybean cultivars.

    Science.gov (United States)

    Salloum, M S; Guzzo, M C; Velazquez, M S; Sagadin, M B; Luna, C M

    2016-12-01

    Breeding selection of germplasm under fertilized conditions may reduce the frequency of genes that promote mycorrhizal associations. This study was developed to compare variability in mycorrhizal colonization and its effect on mycorrhizal dependency (MD) in improved soybean genotypes (I-1 and I-2) with differential tolerance to drought stress, and in unimproved soybean genotypes (UI-3 and UI-4). As inoculum, a mixed native arbuscular mycorrhizal fungi (AMF) was isolated from soybean roots, showing spores mostly of the species Funneliformis mosseae. At 20 days, unimproved genotypes followed by I-2, showed an increase in arbuscule formation, but not in I-1. At 40 days, mycorrhizal plants showed an increase in nodulation, this effect being more evident in unimproved genotypes. Mycorrhizal dependency, evaluated as growth and biochemical parameters from oxidative stress was increased in unimproved and I-2 since 20 days, whereas in I-1, MD increased at 40 days. We cannot distinguish significant differences in AMF colonization and MD between unimproved and I-2. However, variability among improved genotypes was observed. Our results suggest that selection for improved soybean genotypes with good and rapid AMF colonization, particularly high arbuscule/hyphae ratio could be a useful strategy for the development of genotypes that optimize AMF contribution to cropping systems.

  17. Chemical Variability and Biological Activities of Brassica rapa var. rapifera Parts Essential Oils Depending on Geographic Variation and Extraction Technique.

    Science.gov (United States)

    Saka, Boualem; Djouahri, Abderrahmane; Djerrad, Zineb; Terfi, Souhila; Aberrane, Sihem; Sabaou, Nasserdine; Baaliouamer, Aoumeur; Boudarene, Lynda

    2017-06-01

    In the present work, the Brassica rapa var. rapifera parts essential oils and their antioxidant and antimicrobial activities were investigated for the first time depending on geographic origin and extraction technique. Gas-chromatography (GC) and GC/mass spectrometry (MS) analyses showed several constituents, including alcohols, aldehydes, esters, ketones, norisoprenoids, terpenic, nitrogen and sulphur compounds, totalizing 38 and 41 compounds in leaves and root essential oils, respectively. Nitrogen compounds were the main volatiles in leaves essential oils and sulphur compounds were the main volatiles in root essential oils. Qualitative and quantitative differences were found among B. rapa var. rapifera parts essential oils collected from different locations and extracted by hydrodistillation and microwave-assisted hydrodistillation techniques. Furthermore, our findings showed a high variability for both antioxidant and antimicrobial activities. The highlighted variability reflects the high impact of plant part, geographic variation and extraction technique on chemical composition and biological activities, which led to conclude that we should select essential oils to be investigated carefully depending on these factors, in order to isolate the bioactive components or to have the best quality of essential oil in terms of biological activities and preventive effects in food. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  18. Effects of heat loss as percentage of fuel's energy, friction and variable specific heats of working fluid on performance of air standard Otto cycle

    International Nuclear Information System (INIS)

    Lin, J.-C.; Hou, S.-S.

    2008-01-01

    The objective of this study is to analyze the effects of heat loss characterized by a percentage of the fuel's energy, friction and variable specific heats of working fluid on the performance of an air standard Otto cycle with a restriction of maximum cycle temperature. A more realistic and precise relationship between the fuel's chemical energy and the heat leakage that is based on a pair of inequalities is derived through the resulting temperature. The variations in power output and thermal efficiency with compression ratio, and the relations between the power output and the thermal efficiency of the cycle are presented. The results show that the power output as well as the efficiency where maximum power output occurs will increase with increase of the maximum cycle temperature. The temperature dependent specific heats of the working fluid have a significant influence on the performance. The power output and the working range of the cycle increase with the increase of specific heats of the working fluid, while the efficiency decreases with the increase of specific heats of the working fluid. The friction loss has a negative effect on the performance. Therefore, the power output and efficiency of the cycle decrease with increasing friction loss. It is noteworthy that the effects of heat loss characterized by a percentage of the fuel's energy, friction and variable specific heats of the working fluid on the performance of an Otto cycle engine are significant and should be considered in practical cycle analysis. The results obtained in the present study are of importance to provide good guidance for performance evaluation and improvement of practical Otto engines

  19. Are there gender differences in locus of control specific to alcohol dependence?

    Science.gov (United States)

    McPherson, Andrew; Martin, Colin R

    2017-01-01

    To investigate gender differences in locus of control in an alcohol-dependent population. Locus of control helps to explain behaviour in terms of internal (the individual is responsible) or external (outside forces, such as significant other people or chance, are responsible) elements. Past research on gender differences in locus of control in relation to alcohol dependence has shown mixed results. There is a need then to examine gender and locus of control in relation to alcohol dependence to ascertain the veracity of any locus of control differences as a function of gender. The Multidimensional Health Locus of Control form-C was administered to clients from alcohol dependence treatment centres in the West of Scotland. Independent t-tests were carried out to assess gender differences in alcohol dependence severity and internal/external aspects of locus of control. One hundred and eighty-eight (53% females) participants were recruited from a variety of alcohol dependence treatment centres. The majority of participants (72%) came from Alcoholics Anonymous groups. Women revealed a greater internal locus of control compared with men. Women also had a greater 'significant others' locus of control score than men. Men were more reliant on 'chance' and 'doctors' than women. All these trends were not, however, statistically significant. Gender differences in relation to locus of control and alcohol dependence from past studies are ambiguous. This study also found no clear statistically significant differences in locus of control orientation as a function of gender. This article helps nurses to contextualise health behaviours as a result of internal or external forces. It also helps nursing staff to better understand alcohol dependence treatment in relation to self-efficacy and control. Moreover, it highlights an important concept in health education theory. © 2016 John Wiley & Sons Ltd.

  20. Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

    Directory of Open Access Journals (Sweden)

    Philip Gemmell

    Full Text Available Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+, inward rectifying K(+, L-type Ca(2+, and Na(+/K(+ pump currents in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al. at multiple cycle lengths (400, 600, 1,000 ms was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in

  1. Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

    Science.gov (United States)

    Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally

  2. Nonadjacent Dependency Learning in Cantonese-Speaking Children With and Without a History of Specific Language Impairment.

    Science.gov (United States)

    Iao, Lai-Sang; Ng, Lai Yan; Wong, Anita Mei Yin; Lee, Oi Ting

    2017-03-01

    This study investigated nonadjacent dependency learning in Cantonese-speaking children with and without a history of specific language impairment (SLI) in an artificial linguistic context. Sixteen Cantonese-speaking children with a history of SLI and 16 Cantonese-speaking children with typical language development (TLD) were tested with a nonadjacent dependency learning task using artificial languages that mimic Cantonese. Children with TLD performed above chance and were able to discriminate between trained and untrained nonadjacent dependencies. However, children with a history of SLI performed at chance and were not able to differentiate trained versus untrained nonadjacent dependencies. These findings, together with previous findings from English-speaking adults and adolescents with language impairments, suggest that individuals with atypical language development, regardless of age, diagnostic status, language, and culture, show difficulties in learning nonadjacent dependencies. This study provides evidence for early impairments to statistical learning in individuals with atypical language development.

  3. Evaluating the Impact of Antibiotic Exposures as Time-Dependent Variables on the Acquisition of Carbapenem-Resistant Acinetobacter baumannii.

    Science.gov (United States)

    Munoz-Price, L Silvia; Rosa, Rossana; Castro, Jose G; Laowansiri, Panthipa; Latibeaudiere, Rachel; Namias, Nicholas; Tarima, Sergey

    2016-10-01

    To determine the time-dependent effect of antibiotics on the initial acquisition of carbapenem-resistant Acinetobacter baumannii. Retrospective cohort study. Forty-bed trauma ICU in Miami, FL. All consecutive patients admitted to the unit from November 1, 2010, to November 30, 2011. None. Patients underwent surveillance cultures at admission to the unit and weekly thereafter. The primary outcome was the acquisition of carbapenem-resistant A. baumannii on surveillance cultures. Daily antibiotic exposures during the time of observation were used to construct time-dependent variables, including cumulative exposures (in grams and daily observed doses [defined daily doses]). Among 360 patients, 45 (12.5%) became colonized with carbapenem-resistant A. baumannii. Adjusted Cox models showed that each additional point in the Acute Physiologic and Chronic Health Evaluation score increased the hazard by 4.8% (hazard ratio, 1.048; 95% CI, 1.010-1.087; p = 0.0124) and time-dependent exposure to carbapenems quadrupled the hazard (hazard ratio, 4.087; 95% CI, 1.873-8.920; p = 0.0004) of acquiring carbapenem-resistant A. baumannii. Additionally, adjusted Cox models determined that every additional carbapenem defined daily dose increased the hazard of acquiring carbapenem-resistant A. baumannii by 5.1% (hazard ratio, 1.051; 95% CI, 1.007-1.093; p = 0.0243). Carbapenem exposure quadrupled the hazards of acquiring A. baumannii even after controlling for severity of illness.

  4. Demographic models reveal the shape of density dependence for a specialist insect herbivore on variable host plants.

    Science.gov (United States)

    Miller, Tom E X

    2007-07-01

    1. It is widely accepted that density-dependent processes play an important role in most natural populations. However, persistent challenges in our understanding of density-dependent population dynamics include evaluating the shape of the relationship between density and demographic rates (linear, concave, convex), and identifying extrinsic factors that can mediate this relationship. 2. I studied the population dynamics of the cactus bug Narnia pallidicornis on host plants (Opuntia imbricata) that varied naturally in relative reproductive effort (RRE, the proportion of meristems allocated to reproduction), an important plant quality trait. I manipulated per-plant cactus bug densities, quantified subsequent dynamics, and fit stage-structured models to the experimental data to ask if and how density influences demographic parameters. 3. In the field experiment, I found that populations with variable starting densities quickly converged upon similar growth trajectories. In the model-fitting analyses, the data strongly supported a model that defined the juvenile cactus bug retention parameter (joint probability of surviving and not dispersing) as a nonlinear decreasing function of density. The estimated shape of this relationship shifted from concave to convex with increasing host-plant RRE. 4. The results demonstrate that host-plant traits are critical sources of variation in the strength and shape of density dependence in insects, and highlight the utility of integrated experimental-theoretical approaches for identifying processes underlying patterns of change in natural populations.

  5. Specific features of the temperature dependence of the exciton absorption integral in CdS crystals

    International Nuclear Information System (INIS)

    Novikov, A.B.; Solov'ev, L.E.; Talalaev, V.G.

    1986-01-01

    Cadmium sulfide crystals 0.4-2 μm thick in the 4.2-120 K temperature range are investigated experimentally. The shape of the first exciton absorption line in CdS and dependence of integral exciton absorption factor (IEAF) on the quenching constant j are calculated. Rapid growth of the absorption factor in the maximum of the absorption line and decrease of halfwidth of the factor are shown to take place with j increase. The calculation has disclosed that the Bouguer law is observed excluding negligible IEAF oscillations at variation of crystal thickness. Non-monotonous temperature dependence of IEAF is disclosed in some investigated samples; it, obviously, testifies to non-monotonous temperature dependence of j. Depolarization of the absorption line of high-energy exciton states with n=2 and n=3 is discovered in some samples for the first time

  6. Mirror-drawing skill in children with specific language impairment: Improving generalization by incorporating variability into the practice session.

    Science.gov (United States)

    Desmottes, Lise; Maillart, Christelle; Meulemans, Thierry

    2017-05-01

    This study aimed to investigate the procedural deficit hypothesis (PDH) in children with specific language impairment (SLI) by using a mirror-drawing task, a sensorimotor adaptation paradigm that does not involve sequence learning and has never before been used in SLI. A total of 30 school-aged children with SLI matched to 30 typically developing (TD) control children had to trace several figures seen only in mirror-reversed view in two practice sessions separated by a one-week interval. Two practice conditions were compared: a constant condition in which children had to trace the same figure throughout the learning trials, and a variable one in which they had to trace different figures in each trial. The results revealed a similar learning pattern between SLI and TD children in both practice conditions, suggesting that initial learning for a non-sequential procedural task is preserved in SLI. However, the children with SLI generalized the mirror-drawing skill in the same way as the TD children only if there was variability in the way the material was trained (variable practice). No significant schedule effects were observed in the control group.

  7. Resistor capacitor, primitive variable solution of buoyant fluid flow within an enclosure with highly temperature dependent viscosity

    Energy Technology Data Exchange (ETDEWEB)

    Burns, S.P. [Texas Univ., Austin, TX (United States); Gianoulakis, S.E. [Sandia National Labs., Albuquerque, NM (United States)

    1995-07-01

    A numerical solution for buoyant natural convection within a square enclosure containing a fluid with highly temperature dependent viscosity is presented. Although the fluid properties employed do not represent any real fluid, the large variation in the fluid viscosity with temperature is characteristic of turbulent flow modeling with eddy-viscosity concepts. Results are obtained using a primitive variable formulation and the resistor method. The results presented include velocity, temperature and pressure distributions within the enclosure as well as shear stress and heat flux distributions along the enclosure walls. Three mesh refinements were employed and uncertainty values are suggested for the final mesh refinement. These solutions are part of a contributed benchmark solution set for the subject problem.

  8. A specific primed immune response in Drosophila is dependent on phagocytes.

    Directory of Open Access Journals (Sweden)

    Linh N Pham

    2007-03-01

    Full Text Available Drosophila melanogaster, like other invertebrates, relies solely on its innate immune response to fight invading microbes; by definition, innate immunity lacks adaptive characteristics. However, we show here that priming Drosophila with a sublethal dose of Streptococcus pneumoniae protects against an otherwise-lethal second challenge of S. pneumoniae. This protective effect exhibits coarse specificity for S. pneumoniae and persists for the life of the fly. Although not all microbial challenges induced this specific primed response, we find that a similar specific protection can be elicited by Beauveria bassiana, a natural fly pathogen. To characterize this primed response, we focused on S. pneumoniae-induced protection. The mechanism underlying this protective effect requires phagocytes and the Toll pathway. However, activation of the Toll pathway is not sufficient for priming-induced protection. This work contradicts the paradigm that insect immune responses cannot adapt and will promote the search for similar responses overlooked in organisms with an adaptive immune response.

  9. Complement-dependent pathogenicity of brain-specific antibodies in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Khorooshi, Reza; Lillevang, Søren T

    2013-01-01

    The specificity and potential pathogenicity of autoantibodies vary between neurological diseases. It is often unclear whether their detection in cerebrospinal fluid (CSF) is a consequence or a cause of pathology. The goal was to test whether administration of brain-specific antibodies into CSF...... would be sufficient for pathology. Purified immunoglobulin G from a neuromyelitis optica patient was injected intrathecally with complement to naive mice. Histopathological analysis at 7 days revealed damage to the ependyma, disruption of the CSF parenchymal barrier and pathologic lesions, distant from...

  10. Tolerance of Escherichia coli to fluoroquinolone antibiotics depends on specific components of the SOS response pathway.

    Science.gov (United States)

    Theodore, Alyssa; Lewis, Kim; Vulic, Marin

    2013-12-01

    Bacteria exposed to bactericidal fluoroquinolone (FQ) antibiotics can survive without becoming genetically resistant. Survival of these phenotypically resistant cells, commonly called "persisters," depends on the SOS gene network. We have examined mutants in all known SOS-regulated genes to identify functions essential for tolerance in Escherichia coli. The absence of DinG and UvrD helicases and the Holliday junction processing enzymes RuvA and RuvB leads to a decrease in survival. Analysis of the respective mutants indicates that, in addition to repair of double-strand breaks, tolerance depends on the repair of collapsed replication forks and stalled transcription complexes. Mutation in recF results in increased survival, which identifies RecAF recombination as a poisoning mechanism not previously linked to FQ lethality. DinG acts upstream of SOS promoting its induction, whereas RuvAB participates in repair only. UvrD directly promotes all repair processes initiated by FQ-induced damage and prevents RecAF-dependent misrepair, making it one of the crucial SOS functions required for tolerance.

  11. Specific fission J-window and angular momentum dependence of the fission barrier

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Hiroshi; Saito, Tadashi; Takahashi, Naruto; Yokoyama, Akihiko [Osaka Univ., Suita (Japan); Shinohara, Atsushi

    1997-04-01

    A method to determine a unique J-window in the fission process was devised and the fissioning nuclide associated with thus extracted J-window was identified for each of the heavy-ion reaction systems. Obtained fission barriers at the resulting J-window were compared with the calculated values by the rotating finite range model (RFRM). The deduced barriers for individual nuclides were compared with the RFRM barriers to reproduce more or less the angular momentum dependence the RFRM prediction. The deduced systematic behavior of the fission barrier indicates no even-odd and shell corrections are necessary. The nuclear dissipation effect based on Kramer`s model revealed substantial reduction of the statistically deduced barrier heights and brought a fairly large scattering from the RFRM J-dependence. However, introduction of the temperature-dependent friction coefficient ({gamma} = 2 for T {>=} 1.0 MeV and 0.5 for T < 1.0 MeV) was found to bring about satisfactory agreement with both RFRM fission barriers and the pre-fission neutron multiplicity systematics. (author). 81 refs.

  12. Separation of integrin-dependent adhesion from morphological changes based on differential PLC specificities.

    Science.gov (United States)

    Wooten, D K; Teague, T K; McIntyre, B W

    1999-01-01

    In normal lymphocytes an inside-out signal up-regulating integrin adhesion is followed by a ligand-mediated outside-in cell spreading signal. Protein kinase C (PKC) inhibition blocks lymphocyte adherence to and spreading on fibronectin. In contrast, putative PLC inhibitors yield distinct differences with respect to adhesion and morphology. The phosphatidylinositol-specific phospholipase C (PLC) inhibitor neomycin blocked spreading of CD3/CD28-activated T cells on fibronectin by disrupting adhesion. Furthermore, when an additional inside-out signal for fibronectin adhesion is unnecessary such as with HPB-ALL T leukemic or phorbol-myristate-acetate-treated normal T cells, neomycin treatment does not alter adhesion or morphology. However, the phosphatidylcholine-specific PLC inhibitor D609 abrogates cell spreading without affecting adhesion to fibronectin in these cells as well as the CD3/CD28-activated T cells. These results strongly suggest that inside-out signaling for the integrin alpha4beta1 in lymphocytes proceeds through phosphatidylinositol-specific PLC and PKC, whereas the outside-in signal utilizes phosphatidylcholine-specific PLC and PKC.

  13. Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers.

    Science.gov (United States)

    Lanjakornsiripan, Darin; Pior, Baek-Jun; Kawaguchi, Daichi; Furutachi, Shohei; Tahara, Tomoaki; Katsuyama, Yu; Suzuki, Yutaka; Fukazawa, Yugo; Gotoh, Yukiko

    2018-04-24

    Non-pial neocortical astrocytes have historically been thought to comprise largely a nondiverse population of protoplasmic astrocytes. Here we show that astrocytes of the mouse somatosensory cortex manifest layer-specific morphological and molecular differences. Two- and three-dimensional observations revealed that astrocytes in the different layers possess distinct morphologies as reflected by differences in cell orientation, territorial volume, and arborization. The extent of ensheathment of synaptic clefts by astrocytes in layer II/III was greater than that by those in layer VI. Moreover, differences in gene expression were observed between upper-layer and deep-layer astrocytes. Importantly, layer-specific differences in astrocyte properties were abrogated in reeler and Dab1 conditional knockout mice, in which neuronal layers are disturbed, suggesting that neuronal layers are a prerequisite for the observed morphological and molecular differences of neocortical astrocytes. This study thus demonstrates the existence of layer-specific interactions between neurons and astrocytes, which may underlie their layer-specific functions.

  14. Transient Kinetics of a cGMP-dependent cGMP-specific Phosphodiesterase from Dictyostelium discoideum

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Lookeren Campagne, Michiel M. van

    1984-01-01

    Chemotactic stimulation of Dictyostelium discoideum cells induces a fast transient increase of cGMP levels which reach a peak at 10 s. Prestimulation levels are recovered in ~30 s, which is achieved mainly by the action of a guanosine 3',5'-monophosphate cGMP-specific phosphodiesterase. This enzyme

  15. Specific features of time-dependent Psub(N) approximations in spherical geometry

    International Nuclear Information System (INIS)

    Peltzer, P.; Pucker, N.

    1979-01-01

    Approximations to the time-dependent linear transport equation can result in more serious distortions in the description of the actual physical situation than in the stationary problem. This is demonstrated in detail for the case of a neutron pulse in spherical geometry, treated within a P 1 approximation. One has to pay special attention to the singularity at r = 0 and to the effect of the boundary conditions. Effects similar to those shown here are also to be expected in connection with Psub(N) approximations of higher order. (Auth.)

  16. High Prognostic Specificity of Antisocial Personality Disorder in Patients with Drug Dependence

    DEFF Research Database (Denmark)

    Fridell, Mats; Hesse, Morten; Johnson, Eva

    2006-01-01

    personality disorder (ASPD) at intake was associated with incarceration, continuous drug use, dependence on welfare support, and fulfilling criteria of adult ASPD at follow-up. Regardless of ASPD status, a decline was seen in drug-related convictions, but subjects with ASPD were found to continue to commit......A sample of 125 consecutive patients from a Swedish detoxification unit were followed up at five years. Register data on criminal behavior were retrieved for 99% of all subjects, including those who were deceased at follow-up, and 76%of living subjects were interviewed. A diagnosis of antisocial...

  17. Atheroprotective immunization with malondialdehyde-modified LDL is hapten specific and dependent on advanced MDA adducts

    DEFF Research Database (Denmark)

    Gonen, Ayelet; Hansen, Lotte; Turner, William W

    2014-01-01

    as an immunogen would be impractical for generalized use. Furthermore, when MDA is used to modify LDL, a wide variety of related MDA adducts are formed, both simple and more complex. To define the relevant epitopes that would reproduce the atheroprotective effects of immunization with MDA-LDL, we sought......Immunization with homologous malondialdehyde (MDA)-modified LDL (MDA-LDL) leads to atheroprotection in experimental models supporting the concept that a vaccine to oxidation-specific epitopes (OSEs) of oxidized LDL could limit atherogenesis. However, modification of human LDL with OSE to use...... responses. We further demonstrate that a T helper (Th) 2-biased hapten-specific humoral and cellular response is sufficient, and thus, MAA-modified homologous albumin is an equally effective immunogen. We further show that such Th2-biased humoral responses per se are not atheroprotective if they do...

  18. Substrate specificity and pH dependence of homogeneous wheat germ acid phosphatase.

    Science.gov (United States)

    Van Etten, R L; Waymack, P P

    1991-08-01

    The broad substrate specificity of a homogeneous isoenzyme of wheat germ acid phosphatase (WGAP) was extensively investigated by chromatographic, electrophoretic, NMR, and kinetic procedures. WGAP exhibited no divalent metal ion requirement and was unaffected upon incubation with EDTA or o-phenanthroline. A comparison of two catalytically homogeneous isoenzymes revealed little difference in substrate specificity. The specificity of WGAP was established by determining the Michaelis constants for a wide variety of substrates. p-Nitrophenyl phosphate, pyrophosphate, tripolyphosphate, and ATP were preferred substrates while lesser activities were seen toward sugar phosphates, trimetaphosphate, phosphoproteins, and (much less) phosphodiesters. An extensive table of Km and Vmax values is given. The pathway for the hydrolysis of trimetaphosphate was examined by colorimetric and 31P NMR methods and it was found that linear tripolyphosphate is not a free intermediate in the enzymatic reaction. In contrast to literature reports, homogeneous wheat germ acid phosphatase exhibits no measurable carboxylesterase activity, nor does it hydrolyze phenyl phosphonothioate esters or phytic acid at significant rates.

  19. AMPK governs lineage specification through Tfeb-dependent regulation of lysosomes.

    Science.gov (United States)

    Young, Nathan P; Kamireddy, Anwesh; Van Nostrand, Jeanine L; Eichner, Lillian J; Shokhirev, Maxim Nikolaievich; Dayn, Yelena; Shaw, Reuben J

    2016-03-01

    Faithful execution of developmental programs relies on the acquisition of unique cell identities from pluripotent progenitors, a process governed by combinatorial inputs from numerous signaling cascades that ultimately dictate lineage-specific transcriptional outputs. Despite growing evidence that metabolism is integrated with many molecular networks, how pathways that control energy homeostasis may affect cell fate decisions is largely unknown. Here, we show that AMP-activated protein kinase (AMPK), a central metabolic regulator, plays critical roles in lineage specification. Although AMPK-deficient embryonic stem cells (ESCs) were normal in the pluripotent state, these cells displayed profound defects upon differentiation, failing to generate chimeric embryos and preferentially adopting an ectodermal fate at the expense of the endoderm during embryoid body (EB) formation. AMPK(-/-) EBs exhibited reduced levels of Tfeb, a master transcriptional regulator of lysosomes, leading to diminished endolysosomal function. Remarkably, genetic loss of Tfeb also yielded endodermal defects, while AMPK-null ESCs overexpressing this transcription factor normalized their differential potential, revealing an intimate connection between Tfeb/lysosomes and germ layer specification. The compromised endolysosomal system resulting from AMPK or Tfeb inactivation blunted Wnt signaling, while up-regulating this pathway restored expression of endodermal markers. Collectively, these results uncover the AMPK pathway as a novel regulator of cell fate determination during differentiation. © 2016 Young et al.; Published by Cold Spring Harbor Laboratory Press.

  20. Association of Seasonal Climate Variability and Age-Specific Mortality in Northern Sweden before the Onset of Industrialization

    Directory of Open Access Journals (Sweden)

    Joacim Rocklöv

    2014-07-01

    Full Text Available Background and aims: Little is known about health impacts of climate in pre-industrial societies. We used historical data to investigate the association of temperature and precipitation with total and age-specific mortality in Skellefteå, northern Sweden, between 1749 and 1859. Methods: We retrieved digitized aggregated population data of the Skellefteå parish, and monthly temperature and precipitation measures. A generalized linear model was established for year to year variability in deaths by annual and seasonal average temperature and cumulative precipitation using a negative binomial function, accounting for long-term trends in population size. The final full model included temperature and precipitation of all four seasons simultaneously. Relative risks (RR with 95% confidence intervals (CI were calculated for total, sex- and age-specific mortality. Results: In the full model, only autumn precipitation proved statistically significant (RR 1.02; CI 1.00–1.03, per 1cm increase of autumn precipitation, while winter temperature (RR 0.98; CI 0.95–1.00, per 1 °C increase in temperature and spring precipitation (RR 0.98; CI 0.97–1.00 per 1 cm increase in precipitation approached significance. Similar effects were observed for men and women. The impact of climate variability on mortality was strongest in children aged 3–9, and partly also in older children. Infants, on the other hand, appeared to be less affected by unfavourable climate conditions. Conclusions: In this pre-industrial rural region in northern Sweden, higher levels of rain during the autumn increased the annual number of deaths. Harvest quality might be one critical factor in the causal pathway, affecting nutritional status and susceptibility to infectious diseases. Autumn rain probably also contributed to the spread of air-borne diseases in crowded living conditions. Children beyond infancy appeared most vulnerable to climate impacts.

  1. Pressure dependence of the specific heat of heavy-fermion YbCu4.5

    International Nuclear Information System (INIS)

    Amato, A.; Fisher, R.A.; Phillips, N.E.; Jaccard, D.; Walker, E.

    1990-03-01

    The specific heat of a polycrystalline sample of YbCu 4.5 has been measured between 0.3 and 20K at pressures to 8.2 kbar. Unlike cerium-based heavy-fermion compounds, an increase of C/T is observed with increasing pressure, with the linear term enhanced by about 16% at 8.2 kbar. Above 7K, (∂C/∂P) T is negative. The nuclear contribution observed at P = 0 is increased by roughly a factor of two at 8.2 kbar. 7 refs., 3 figs

  2. Herbivore-specific, density-dependent induction of plant volatiles: honest or "cry wolf" signals?

    Directory of Open Access Journals (Sweden)

    Kaori Shiojiri

    Full Text Available Plants release volatile chemicals upon attack by herbivorous arthropods. They do so commonly in a dose-dependent manner: the more herbivores, the more volatiles released. The volatiles attract predatory arthropods and the amount determines the probability of predator response. We show that seedlings of a cabbage variety (Brassica oleracea var. capitata, cv Shikidori also show such a response to the density of cabbage white (Pieris rapae larvae and attract more (naive parasitoids (Cotesia glomerata when there are more herbivores on the plant. However, when attacked by diamondback moth (Plutella xylostella larvae, seedlings of the same variety (cv Shikidori release volatiles, the total amount of which is high and constant and thus independent of caterpillar density, and naive parasitoids (Cotesia vestalis of diamondback moth larvae fail to discriminate herbivore-rich from herbivore-poor plants. In contrast, seedlings of another cabbage variety of B. oleracea (var. acephala: kale respond in a dose-dependent manner to the density of diamondback moth larvae and attract more parasitoids when there are more herbivores. Assuming these responses of the cabbage cultivars reflect behaviour of at least some genotypes of wild plants, we provide arguments why the behaviour of kale (B. oleracea var acephala is best interpreted as an honest signaling strategy and that of cabbage cv Shikidori (B. oleracea var capitata as a "cry wolf" signaling strategy, implying a conflict of interest between the plant and the enemies of its herbivores: the plant profits from being visited by the herbivore's enemies, but the latter would be better off by visiting other plants with more herbivores. If so, evolutionary theory on alarm signaling predicts consequences of major interest to students of plant protection, tritrophic systems and communication alike.

  3. Sleep Dependent Synaptic Down-Selection (II: Single Neuron Level Benefits for Matching, Selectivity, and Specificity

    Directory of Open Access Journals (Sweden)

    Atif eHashmi

    2013-10-01

    Full Text Available In a companion paper (Nere et al., this volume, we used computer simulations to show that a strategy of activity-dependent, on-line net synaptic potentiation during wake, followed by off-line synaptic depression during sleep, can provide a parsimonious account for several memory benefits of sleep at the systems level, including the consolidation of procedural and declarative memories, gist extraction, and integration of new with old memories. In this paper, we consider the theoretical benefits of this two-step process at the single neuron level and employ the theoretical notion of Matching between brain and environment to measure how this process increases the ability of the neuron to capture regularities in the environment and model them internally. We show that down-selection during sleep is beneficial for increasing or restoring Matching after learning, after integrating new with old memories, and after forgetting irrelevant material. By contrast, alternative schemes, such as additional potentiation in wake, potentiation in sleep, or synaptic renormalization in wake, decrease Matching. We also argue that, by selecting appropriate loops through the brain that tie feedforward synapses with feedback ones in the same dendritic domain, different subsets of neurons can learn to specialize for different contingencies and form sequences of nested perception-action loops. By potentiating such loops when interacting with the environment in wake, and depressing them when disconnected from the environment in sleep, neurons can learn to match the long-term statistical structure of the environment while avoiding spurious modes of functioning and catastrophic interference. Finally, such a two-step process has the additional benefit of desaturating the neuron's ability to learn and of maintaining cellular homeostasis. Thus, sleep-dependent synaptic renormalization offers a parsimonious account for both cellular and systems-level effects of sleep on learning

  4. Ca2+-dependent proteolytic activity in crab claw muscle: effects of inhibitors and specificity for myofibrillar proteins

    International Nuclear Information System (INIS)

    Mykles, D.L.; Skinner, D.M.

    1983-01-01

    The claw closer muscle of the Bermuda land crab, Gecarcinus lateralis, undergoes a sequential atrophy and restoration during each molting cycle. The role of Ca 2+ -dependent proteinases in the turn-over of myofibrillar protein in normal anecdysial (intermolt) claw muscle is described. Crab Ca 2+ -dependent proteinase degrades the myofibrillar proteins actin, myosin heavy and light chains, paramyosin, tropomyosin, and troponin-T and -I. Ca 2+ -dependent proteinase activity in whole homogenates and 90,000 x g supernatant fractions from muscle homogenates has been characterized with respect to Ca 2+ requirement, substrate specificity, and effects of proteinase inhibitors. The enzyme is inhibited by antipain, leupeptin, E-64, and iodoacetamide; it is insensitive to pepstatin A. The specificity of crab Ca 2+ -dependent proteinase was examined with native myosin with normal ATPase activity as well as with radioiodinated myosin and radioiodinated hemolymph proteins. Hydrolysis of 125 I-myosin occurs in two phases, both Ca 2+ -dependent: (1) heavy chain (M/sub r/ = 200,000) is cleaved into four large fragments (M/sub r/ = 160,000, 110,000, 73,000, 60,000) and numerous smaller fragments; light chain (M/sub r/ = 18,000) is cleaved to a 15,000-Da fragment; (2) the fragments produced in the first phase are hydrolyzed to acid-soluble material. Although radioiodinated native hemolymph proteins are not susceptible to the Ca 2+ -dependent proteinase, those denatured by carboxymethylation are degraded. These data suggest that crab Ca 2+ -dependent proteinase is involved in turnover of myofibrillar protein in normal muscle and muscle undergoing proecdysial atrophy

  5. Host-Specific and pH-Dependent Microbiomes of Copepods in an Extensive Rearing System.

    Science.gov (United States)

    Skovgaard, Alf; Castro-Mejia, Josue Leonardo; Hansen, Lars Hestbjerg; Nielsen, Dennis Sandris

    2015-01-01

    Copepods are to an increasing extent cultivated as feed for mariculture fish larvae with variable production success. In the temperate climate zone, this production faces seasonal limitation due to changing abiotic factors, in particular temperature and light. Furthermore, the production of copepods may be influenced by biotic factors of the culture systems, such as competing microorganisms, harmful algae, or other eukaryotes and prokaryotes that may be non-beneficial for the copepods. In this study, the composition of bacteria associated with copepods was investigated in an extensive outdoor copepod production system. Light microscopy and scanning electron microscopy revealed that bacteria were primarily found attached to the exoskeleton of copepods although a few bacteria were also found in the gut as well as internally in skeletal muscle tissue. Through 16S rRNA gene-targeted denaturing gradient gel electrophoresis (DGGE) analysis, a clear difference was found between the microbiomes of the two copepod species, Acartia tonsa and Centropages hamatus, present in the system. This pattern was corroborated through 454/FLX-based 16S rRNA gene amplicon sequencing of copepod microbiomes, which furthermore showed that the abiotic parameters pH and oxygen concentration in rearing tank water were the key factors influencing composition of copepod microbiomes.

  6. Host-Specific and pH-Dependent Microbiomes of Copepods in an Extensive Rearing System.

    Directory of Open Access Journals (Sweden)

    Alf Skovgaard

    Full Text Available Copepods are to an increasing extent cultivated as feed for mariculture fish larvae with variable production success. In the temperate climate zone, this production faces seasonal limitation due to changing abiotic factors, in particular temperature and light. Furthermore, the production of copepods may be influenced by biotic factors of the culture systems, such as competing microorganisms, harmful algae, or other eukaryotes and prokaryotes that may be non-beneficial for the copepods. In this study, the composition of bacteria associated with copepods was investigated in an extensive outdoor copepod production system. Light microscopy and scanning electron microscopy revealed that bacteria were primarily found attached to the exoskeleton of copepods although a few bacteria were also found in the gut as well as internally in skeletal muscle tissue. Through 16S rRNA gene-targeted denaturing gradient gel electrophoresis (DGGE analysis, a clear difference was found between the microbiomes of the two copepod species, Acartia tonsa and Centropages hamatus, present in the system. This pattern was corroborated through 454/FLX-based 16S rRNA gene amplicon sequencing of copepod microbiomes, which furthermore showed that the abiotic parameters pH and oxygen concentration in rearing tank water were the key factors influencing composition of copepod microbiomes.

  7. SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Ma, L; Braunstein, S; Chiu, J [University of California San Francisco, San Francisco, CA (United States); Sahgal, A [Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario (Canada)

    2016-06-15

    Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive an EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.

  8. Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.

    Directory of Open Access Journals (Sweden)

    Sylvie Lachmann

    Full Text Available The mammalian protein kinase N (PKN family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.

  9. Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.

    Science.gov (United States)

    Lachmann, Sylvie; Jevons, Amy; De Rycker, Manu; Casamassima, Adele; Radtke, Simone; Collazos, Alejandra; Parker, Peter J

    2011-01-01

    The mammalian protein kinase N (PKN) family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s) of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.

  10. A new method to detect transitory signatures and local time/space variability structures in the climate system: the scale-dependent correlation analysis

    Science.gov (United States)

    Rodó, Xavier; Rodríguez-Arias, Miquel-Àngel

    2006-10-01

    The study of transitory signals and local variability structures in both/either time and space and their role as sources of climatic memory, is an important but often neglected topic in climate research despite its obvious importance and extensive coverage in the literature. Transitory signals arise either from non-linearities, in the climate system, transitory atmosphere-ocean couplings, and other processes in the climate system evolving after a critical threshold is crossed. These temporary interactions that, though intense, may not last long, can be responsible for a large amount of unexplained variability but are normally considered of limited relevance and often, discarded. With most of the current techniques at hand these typology of signatures are difficult to isolate because the low signal-to-noise ratio in midlatitudes, the limited recurrence of the transitory signals during a customary interval of data considered. Also, there is often a serious problem arising from the smoothing of local or transitory processes if statistical techniques are applied, that consider all the length of data available, rather than taking into account the size of the specific variability structure under investigation. Scale-dependent correlation (SDC) analysis is a new statistical method capable of highlighting the presence of transitory processes, these former being understood as temporary significant lag-dependent autocovariance in a single series, or covariance structures between two series. This approach, therefore, complements other approaches such as those resulting from the families of wavelet analysis, singular-spectrum analysis and recurrence plots. A main feature of SDC is its high-performance for short time series, its ability to characterize phase-relationships and thresholds in the bivariate domain. Ultimately, SDC helps tracking short-lagged relationships among processes that locally or temporarily couple and uncouple. The use of SDC is illustrated in the present

  11. Free energy of activation. Definition, properties, and dependent variables with special reference to linear free energy relations

    International Nuclear Information System (INIS)

    Levine, R.D.

    1979-01-01

    The reaction rate constant is expressed as Z exp(-G/sub a//RT). Z is the binary collision frequency. G/sub a/, the free energy of activation, is shown to be the difference between the free energy of the reactive reactants and the free energy of all reactants. The results are derived from both a statistical mechanical and a collision theoretic point of view. While the later is more suitable for an ab-initio computation of the reaction rate, it is the former that lends itself to the search of systematics and of correlations and to compaction of data. Different thermodynamic-like routes to the characterization of G/sub a/ are thus explored. The two most promising ones appear to be the use of thermodynamic type cycles and the changes of dependent variables using the Legendre transform technique. The dependence of G/sub a/ on ΔG 0 , the standard free energy change in the reaction, is examined from the later point of view. It is shown that one can rigorously express this dependence as G/sub a/ = αΔG 0 + G/sub a/ 0 M(α). Here α is the Bronsted slope, α = -par. delta ln k(T)/par. delta(ΔG 0 /RT), G/sub a/ 0 is independent of ΔG 0 and M(α), the Legendre transform of G/sub a/, is a function only of α. For small changes in ΔG 0 , the general result reduces to the familiar ''linear'' free energy relation delta G/sub a/ = α delta ΔG 0 . It is concluded from general considerations that M(α) is a symmetric, convex function of α and hence that α is a monotonically increasing function of ΔG 0 . Experimental data appear to conform well to the form α = 1/[1 + exp(-ΔG 0 /G/sub s/ 0 )]. A simple interpretation of the ΔG 0 dependence of G/sub a/, based on an interpolation of the free energy from that of the reagents to that of the products, is offered. 4 figures, 69 references

  12. Variability of Pinus halepensis Mill. Essential Oils and Their Antioxidant Activities Depending on the Stage of Growth During Vegetative Cycle.

    Science.gov (United States)

    Djerrad, Zineb; Djouahri, Abderrahmane; Kadik, Leila

    2017-04-01

    The impact of growth stages during vegetative cycle (B 0  - B 5 ) on chemical composition and antioxidant activities of Pinus halepensis Mill. needles essential oils was investigated for the first time. GC and GC/MS analyses pointed to a quantitative variability of components; terpene hydrocarbons derivatives, represented by α-pinene (8.5 - 12.9%), myrcene (17.5 - 21.6%), p-cymene (7.9 - 11.9%) and (Z)-β-caryophyllene (17.3 - 21.2%) as major components, decreased from 88.9% at B 0 growth stage to 66.9% at B 5 growth stage, whereas oxygenated derivatives, represented by caryophyllene oxide (5.4 - 12.6%) and terpinen-4-ol (0.4 - 3.3%) as major components, increased from 7% at B 0 growth stage to 28.4% at B 5 growth stage. Furthermore, our findings showed that essential oil of P. halepensis needles collected at B 5 growth stage possess higher antioxidant activities by four different testing systems than those collected at B 0  - B 4 growth stages. This highlighted variability led to conclude that we should select essential oils to be investigated carefully depending on growth stage, in order to have the highest effectiveness of essential oil in terms of biological activities for human health purposes. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  13. Moisture Dependence of physical Properties and Specific Heat Capacity of Neem (Azadirachta Indica A. Juss Kernels

    Directory of Open Access Journals (Sweden)

    A. Dauda

    2017-02-01

    Full Text Available This study investigated the effect of moisture content on the physical properties and specific heat capacity of Neem (Azadirachta Indica A. Juss nut kernels. The major, intermediate and minor axial dimensions of the kernels increased from 1.04 to 1.23cm, 0.42 to 0.6cm, and 0.32 to 0.45cm respectively, as the moisture content increased from 5.2 to 44.9 % (db. The arithmetic and geometric mean diameters determined at the same moisture level were significantly different from each other, with the arithmetic mean diameter being higher. In the above moisture range, one thousand kernel weight, true density, porosity, sphericity, roundness and surface area all increased linearly from 0.0987 to 0.1755kg, 632 to 733kgm-3, 6.42 to 32.14%, 41.3 to 47.5%, 22 to 36% and 13 to 24cm2 respectively, while bulk density decreased from 591.4 to 497.4kgm-3 with increase in moisture content. Angle of repose increased from 21.22 to 29.8o with increase in moisture content. The Static coefficient of friction on ply wood with grains parallel to the direction of movement ranged from 0.41 to 0.61, it ranged from 0.19 to 0.24 on on fiber glass, 0.28 to .038 on hessian bag material and 0.25 to 0.33 on galvanized steel sheet. The specific heat of the seed varied from 2738.1- 4345.4J/kg/oC in the above moisture range.

  14. Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets.

    Science.gov (United States)

    Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

    2015-09-01

    Present research deals with the development of compression-coated flurbiprofen colon-targeted tablets to retard the drug release in the upper gastro intestinal system, but progressively release the drug in the colon. Flurbiprofen core tablets were prepared by direct compression method and were compression coated using sodium alginate and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. The optimized formulation showed negligible drug release (4.33 ± 0.06 %) in the initial lag period followed by progressive release (100.78 ± 0.64 %) for 24 h. The X-ray imaging in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C max of colon-targeted tablets was 12,374.67 ng/ml at T max 10 h, where as in case of immediate release tablets the C max was 15,677.52 ng/ml at T max 3 h, that signifies the ability of compression-coated tablets to target the colon. Development of compression-coated tablets using combination of time-dependent and pH-sensitive approaches was suitable to target the flurbiprofen to colon.

  15. Influence of Flow Sequencing Attributed to Climate Change and Climate Variability on the Assessment of Water-dependent Ecosystem Outcomes

    Science.gov (United States)

    Wang, J.; Nathan, R.; Horne, A.

    2017-12-01

    Traditional approaches to characterize water-dependent ecosystem outcomes in response to flow have been based on time-averaged hydrological indicators, however there is increasing recognition for the need to characterize ecological processes that are highly dependent on the sequencing of flow conditions (i.e. floods and droughts). This study considers the representation of flow regimes when considering assessment of ecological outcomes, and in particular, the need to account for sequencing and variability of flow. We conducted two case studies - one in the largely unregulated Ovens River catchment and one in the highly regulated Murray River catchment (both located in south-eastern Australia) - to explore the importance of flow sequencing to the condition of a typical long-lived ecological asset in Australia, the River Red Gum forests. In the first, the Ovens River case study, the implications of representing climate change using different downscaling methods (annual scaling, monthly scaling, quantile mapping, and weather generator method) on the sequencing of flows and resulting ecological outcomes were considered. In the second, the Murray River catchment, sequencing within a historic drought period was considered by systematically making modest adjustments on an annual basis to the hydrological records. In both cases, the condition of River Red Gum forests was assessed using an ecological model that incorporates transitions between ecological conditions in response to sequences of required flow components. The results of both studies show the importance of considering how hydrological alterations are represented when assessing ecological outcomes. The Ovens case study showed that there is significant variation in the predicted ecological outcomes when different downscaling techniques are applied. Similarly, the analysis in the Murray case study showed that the drought as it historically occurred provided one of the best possible outcomes for River Red Gum

  16. IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

    Science.gov (United States)

    Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

    2016-02-01

    Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igf(f/f) mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin-cyclic recombinase [Cre] mice with Igf(f/f) mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro-computed tomography (μCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1-deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin/receptor-activator of NF-κB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data

  17. Possible roles of HIV-1 nucleocapsid protein in the specificity of proviral DNA synthesis and in its variability.

    Science.gov (United States)

    Lapadat-Tapolsky, M; Gabus, C; Rau, M; Darlix, J L

    1997-05-02

    Retroviral nucleocapsid (NC) protein is an integral part of the virion nucleocapsid where it coats the dimeric RNA genome. Due to its nucleic acid binding and annealing activities, NC protein directs the annealing of the tRNA primer to the primer binding site and greatly facilitates minus strand DNA elongation and transfer while protecting the nucleic acids against nuclease degradation. To understand the role of NCp7 in viral DNA synthesis, we examined the influence of NCp7 on self-primed versus primer-specific reverse transcription. The results show that HIV-1 NCp7 can extensively inhibit self-primed reverse transcription of viral and cellular RNAs while promoting primer-specific synthesis of proviral DNA. The role of NCp7 vis-a-vis the presence of mutations in the viral DNA during minus strand elongation was examined. NCp7 maximized the annealing between a cDNA(-) primer containing one to five consecutive errors and an RNA representing the 3' end of the genome. The ability of reverse transcriptase (RT) in the presence of NCp7 to subsequently extend the mutated primers depended upon the position of the mismatch within the primer:template complex. When the mutations were at the polymerisation site, primer extension by RT in the presence of NCp7 was very high, about 40% for one mismatch and 3% for five consecutive mismatches. Mutations within the DNA primer or at its 5' end had little effect on the extension of viral DNA by RT. Taken together these results indicate that NCp7 plays major roles in proviral DNA synthesis within the virion core due to its ability to promote prime-specific proviral DNA synthesis while concurrently inhibiting non-specific reverse transcription of viral and cellular RNAs. Moreover, the observation that NCp7 enhances the incorporation of mutations during minus strand DNA elongation favours the notion that NCp7 is a factor contributing to the high mutation rate of HIV-1.

  18. Patient-Specific Tailored Intervention Improves INR Time in Therapeutic Range and INR Variability in Heart Failure Patients.

    Science.gov (United States)

    Gotsman, Israel; Ezra, Orly; Hirsh Raccah, Bruria; Admon, Dan; Lotan, Chaim; Dekeyser Ganz, Freda

    2017-08-01

    Many patients with heart failure need anticoagulants, including warfarin. Good control is particularly challenging in heart failure patients, with range, thereby increasing the risk of complications. This study aimed to evaluate the effect of a patient-specific tailored intervention on anticoagulation control in patients with heart failure. Patients with heart failure taking warfarin therapy (n = 145) were randomized to either standard care or a 1-time intervention assessing potential risk factors for lability of INR, in which they received patient-specific instructions. Time in therapeutic range (TTR) using Rosendaal's linear model was assessed 3 months before and after the intervention. The patient-tailored intervention significantly increased anticoagulation control. The median TTR levels before intervention were suboptimal in the interventional and control groups (53% vs 45%, P = .14). After intervention the median TTR increased significantly in the interventional group compared with the control group (80% [interquartile range, 62%-93%] vs 44% [29%-61%], P <.0001). The intervention resulted in a significant improvement in the interventional group before versus after intervention (53% vs 80%, P <.0001) but not in the control group (45% vs 44%, P = .95). The percentage of patients with a TTR ≥60%, considered therapeutic, was substantially higher in the interventional group: 79% versus 25% (P <.0001). The INR variability (standard deviation of each patient's INR measurements) decreased significantly in the interventional group, from 0.53 to 0.32 (P <.0001) after intervention but not in the control group. Patient-specific tailored intervention significantly improves anticoagulation therapy in patients with heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Abbreviation as a Reflection of Terms Variability in Language for Specific Purposes: Translational Features (Terminology Case Study in German, English, Kazakh, and Russia)

    Science.gov (United States)

    Beisembayeva, Gulshat Z.; Yeskindirova, Manshuk Z.; Tulebayeva, Samal A.

    2016-01-01

    The range of modern dynamic social changes, globalization of world powers' economic cooperation, acceleration of technocratic processes have widespread impact on term systems' variability in language, in particular, on terminological variability for specific purposes. This globalized extra-linguistic factor provokes avalanche growth of…

  20. DEPENDENCE BETWEEN ACYLATION DEGREE AND SPECIFIC LYSIS ACTITIVY OF THE PSEUDOMONAS AERUGINOSA М6 BACTERIOPHAGE

    Directory of Open Access Journals (Sweden)

    Martynov A. V.

    2016-06-01

    Full Text Available Introduction. The purpose of this work is to study the influence of various degrees of protein’s acylation on lytic activity and other biological properties of Pseudomonas M6 bacteriophage. Materials and methods. The subject of the study were samples of the Pseudomonas O 12 bacteriophage, hereinafter named the M6 phage. Pure phage lines were obtained from individual standard-morphology phage plaques (plaque-forming units, or PFUs after ten passes over the indicator strain. In subsequent experiments, M6 phage samples were selected that had a sufficient level of purity (homogeneous in the morphology of virions that inactivated the homologic antiphage serum by no less than 99.0% and the heterologic antibacterial serum by no more than 1%, and a titer no lower than 10 PFU per ml (PFU/ml. Titration of the phages was conducted using the standard bilayer agar. The crude protein content in the phage suspensions was determined using the spectroscopic method (at 280 and 260 nm. Succinylation of the phage samples was conducted according to the method developed by T.J. Molenaar. The phage’s lytic activity spectrum was determined through spot tests on 224 strains of the Pseudomonas genus and 106 strains of other genera (correspondingly, of strains Enterobacter -40, Escherichia -10, Citrobacter -8, Hafnia -7, Serratia -6, Shigella -10, Salmonella -8, Proteus -7 through the use of a phage suspension containing 10 5 - 10 6 PFU/ml. (This concentration of infectious phage corpuscles corresponds with the critical distribution of the M6 phage. The results of the research were subjected to statistical processing using single-factor dispersion analysis. Results and discussion. One hundred percent phage protein acylation leads to a loss of adsorption ability on sensitive cells and is accompanied by a significant (more than 103 times decrease in the level of specific lytic activity in the phage preparations. The succinylation type being studied does not cause

  1. Inference for binomial probability based on dependent Bernoulli random variables with applications to meta‐analysis and group level studies

    Science.gov (United States)

    Bakbergenuly, Ilyas; Morgenthaler, Stephan

    2016-01-01

    We study bias arising as a result of nonlinear transformations of random variables in random or mixed effects models and its effect on inference in group‐level studies or in meta‐analysis. The findings are illustrated on the example of overdispersed binomial distributions, where we demonstrate considerable biases arising from standard log‐odds and arcsine transformations of the estimated probability p^, both for single‐group studies and in combining results from several groups or studies in meta‐analysis. Our simulations confirm that these biases are linear in ρ, for small values of ρ, the intracluster correlation coefficient. These biases do not depend on the sample sizes or the number of studies K in a meta‐analysis and result in abysmal coverage of the combined effect for large K. We also propose bias‐correction for the arcsine transformation. Our simulations demonstrate that this bias‐correction works well for small values of the intraclass correlation. The methods are applied to two examples of meta‐analyses of prevalence. PMID:27192062

  2. HEART RATE VARIABILITY PARAMETERS IN PATIENTS WITH ARTERIAL HYPERTENSION IN DEPENDENCE ON THE TYPE OF DAILY BLOOD PRESSURE PROFILE

    Directory of Open Access Journals (Sweden)

    S. G. B. K. Gorantla

    2017-06-01

    Full Text Available Violation of functioning of the autonomic nervous system is an important factor in the formation and progression of arterial hypertension (AH. Abnormal nocturnal blood pressure (BP reduction is regarded as an independent prognostic factor for cardiovascular complications in patients with AH. One of the possible factors that determine the violation of BP circadian rhythm can be imbalance of different parts of autonomic nervous system. The aim of our study was to study heart rate variability (HRV in patients with AH, dependently of BP profile. 72 patients with AH were examined. Average age was 57 ± 11 years. All patients underwent ambulatory BP (ABPM and ECG monitoring. To define the daily profile the nocturnal BP dip was quantified and for HRV evaluation the frequency analysis method was used. HRV changes in patients with AH present with reduced total power and with a violation in the ratio of the powers of very low, low and high frequencies, enhanced sympathycotension and influence of humoral factors. Violations of systolic BP (SBP daily profile was mainly characterized by an increase in the power of low frequency waves, which indicates an intensification of sympathetic and decreased parasympathetic influences. Violations of diastolic BP (DBP daily profile were mainly characterized by a relative increase in the power of very low frequency waves. The obtained results showed that in the management of patients with AH it is important not only to control the circadian SBP and DBP profiles, but the evaluation of HRV also.

  3. Inference for binomial probability based on dependent Bernoulli random variables with applications to meta-analysis and group level studies.

    Science.gov (United States)

    Bakbergenuly, Ilyas; Kulinskaya, Elena; Morgenthaler, Stephan

    2016-07-01

    We study bias arising as a result of nonlinear transformations of random variables in random or mixed effects models and its effect on inference in group-level studies or in meta-analysis. The findings are illustrated on the example of overdispersed binomial distributions, where we demonstrate considerable biases arising from standard log-odds and arcsine transformations of the estimated probability p̂, both for single-group studies and in combining results from several groups or studies in meta-analysis. Our simulations confirm that these biases are linear in ρ, for small values of ρ, the intracluster correlation coefficient. These biases do not depend on the sample sizes or the number of studies K in a meta-analysis and result in abysmal coverage of the combined effect for large K. We also propose bias-correction for the arcsine transformation. Our simulations demonstrate that this bias-correction works well for small values of the intraclass correlation. The methods are applied to two examples of meta-analyses of prevalence. © 2016 The Authors. Biometrical Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  4. A numerical model for density-and-viscosity-dependent flows in two-dimensional variably saturated porous media

    Science.gov (United States)

    Boufadel, Michel C.; Suidan, Makram T.; Venosa, Albert D.

    1999-04-01

    We present a formulation for water flow and solute transport in two-dimensional variably saturated media that accounts for the effects of the solute on water density and viscosity. The governing equations are cast in a dimensionless form that depends on six dimensionless groups of parameters. These equations are discretized in space using the Galerkin finite element formulation and integrated in time using the backward Euler scheme with mass lumping. The modified Picard method is used to linearize the water flow equation. The resulting numerical model, the MARUN model, is verified by comparison to published numerical results. It is then used to investigate beach hydraulics at seawater concentration (about 30 g l -1) in the context of nutrients delivery for bioremediation of oil spills on beaches. Numerical simulations that we conducted in a rectangular section of a hypothetical beach revealed that buoyancy in the unsaturated zone is significant in soils that are fine textured, with low anisotropy ratio, and/or exhibiting low physical dispersion. In such situations, application of dissolved nutrients to a contaminated beach in a freshwater solution is superior to their application in a seawater solution. Concentration-engendered viscosity effects were negligible with respect to concentration-engendered density effects for the cases that we considered.

  5. Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Pujuguet, Philippe; Simian, Marina; Liaw, Jane; Timpl, Rupert; Werb, Zena; Bissell, Mina J..

    2000-02-01

    Nidogen-1 (entactin) acts as a bridge between the extracellular matrix molecules laminin-1 and type IV collagen, and thus participates in the assembly of basement membranes. To investigate the role of nidogen-1 in regulating cell-type-specific gene expression in mammary epithelium, we designed a culture microecosystem in which each component, including epithelial cells, mesenchymal cells, lactogenic hormones and extracellular matrix, could be controlled. We found that primary and established mesenchymal and myoepithelial cells synthesized and secreted nidogen-1, whereas expression was absent in primary and established epithelial cells. In an epithelial cell line containing mesenchymal cells, nidogen-1 was produced by the mesenchymal cells but deposited between the epithelial cells. In this mixed culture, mammary epithelial cells express b-casein in the presence of lactogenic hormones. Addition of either laminin-1 plus nidogen-1, or laminin-1 alone to mammary epithelial cells induced b- casein production. We asked whether recombinant nidogen-1 alone could signal directly for b-casein. Nidogen-1 did not induce b-casein synthesis in epithelial cells, but it augmented the inductive capacity of laminin-1. These data suggest that nidogen-1 can cooperate with laminin-1 to regulate b-casein expression. Addition of full length nidogen-1 to the mixed cultures had no effect on b-casein gene expression; however, a nidogen-1 fragment containing the laminin-1 binding domain, but lacking the type IV collagen-binding domain, had a dominant negative effect on b-casein expression. These data point to a physiological role for nidogen-1 in the basement membrane-induced gene expression by epithelial cells.

  6. OptMAVEn--a new framework for the de novo design of antibody variable region models targeting specific antigen epitopes.

    Directory of Open Access Journals (Sweden)

    Tong Li

    Full Text Available Antibody-based therapeutics provides novel and efficacious treatments for a number of diseases. Traditional experimental approaches for designing therapeutic antibodies rely on raising antibodies against a target antigen in an immunized animal or directed evolution of antibodies with low affinity for the desired antigen. However, these methods remain time consuming, cannot target a specific epitope and do not lead to broad design principles informing other studies. Computational design methods can overcome some of these limitations by using biophysics models to rationally select antibody parts that maximize affinity for a target antigen epitope. This has been addressed to some extend by OptCDR for the design of complementary determining regions. Here, we extend this earlier contribution by addressing the de novo design of a model of the entire antibody variable region against a given antigen epitope while safeguarding for immunogenicity (Optimal Method for Antibody Variable region Engineering, OptMAVEn. OptMAVEn simulates in silico the in vivo steps of antibody generation and evolution, and is capable of capturing the critical structural features responsible for affinity maturation of antibodies. In addition, a humanization procedure was developed and incorporated into OptMAVEn to minimize the potential immunogenicity of the designed antibody models. As case studies, OptMAVEn was applied to design models of neutralizing antibodies targeting influenza hemagglutinin and HIV gp120. For both HA and gp120, novel computational antibody models with numerous interactions with their target epitopes were generated. The observed rates of mutations and types of amino acid changes during in silico affinity maturation are consistent with what has been observed during in vivo affinity maturation. The results demonstrate that OptMAVEn can efficiently generate diverse computational antibody models with both optimized binding affinity to antigens and reduced

  7. SPECIES-SPECIFIC FOREST VARIABLE ESTIMATION USING NON-PARAMETRIC MODELING OF MULTI-SPECTRAL PHOTOGRAMMETRIC POINT CLOUD DATA

    Directory of Open Access Journals (Sweden)

    J. Bohlin

    2012-07-01

    Full Text Available The recent development in software for automatic photogrammetric processing of multispectral aerial imagery, and the growing nation-wide availability of Digital Elevation Model (DEM data, are about to revolutionize data capture for forest management planning in Scandinavia. Using only already available aerial imagery and ALS-assessed DEM data, raster estimates of the forest variables mean tree height, basal area, total stem volume, and species-specific stem volumes were produced and evaluated. The study was conducted at a coniferous hemi-boreal test site in southern Sweden (lat. 58° N, long. 13° E. Digital aerial images from the Zeiss/Intergraph Digital Mapping Camera system were used to produce 3D point-cloud data with spectral information. Metrics were calculated for 696 field plots (10 m radius from point-cloud data and used in k-MSN to estimate forest variables. For these stands, the tree height ranged from 1.4 to 33.0 m (18.1 m mean, stem volume from 0 to 829 m3 ha-1 (249 m3 ha-1 mean and basal area from 0 to 62.2 m2 ha-1 (26.1 m2 ha-1 mean, with mean stand size of 2.8 ha. Estimates made using digital aerial images corresponding to the standard acquisition of the Swedish National Land Survey (Lantmäteriet showed RMSEs (in percent of the surveyed stand mean of 7.5% for tree height, 11.4% for basal area, 13.2% for total stem volume, 90.6% for pine stem volume, 26.4 for spruce stem volume, and 72.6% for deciduous stem volume. The results imply that photogrammetric matching of digital aerial images has significant potential for operational use in forestry.

  8. Oxygen-Dependent Cell-to-Cell Variability in the Output of the Escherichia coli Tor Phosphorelay.

    Science.gov (United States)

    Roggiani, Manuela; Goulian, Mark

    2015-06-15

    Escherichia coli senses and responds to trimethylamine-N-oxide (TMAO) in the environment through the TorT-TorS-TorR signal transduction system. The periplasmic protein TorT binds TMAO and stimulates the hybrid kinase TorS to phosphorylate the response regulator TorR through a phosphorelay. Phosphorylated TorR, in turn, activates transcription of the torCAD operon, which encodes the proteins required for anaerobic respiration via reduction of TMAO to trimethylamine. Interestingly, E. coli respires TMAO in both the presence and absence of oxygen, a behavior that is markedly different from the utilization of other alternative electron acceptors by this bacterium. Here we describe an unusual form of regulation by oxygen for this system. While the average level of torCAD transcription is the same for aerobic and anaerobic cultures containing TMAO, the behavior across the population of cells is strikingly different under the two growth conditions. Cellular levels of torCAD transcription in aerobic cultures are highly heterogeneous, in contrast to the relatively homogeneous distribution in anaerobic cultures. Thus, oxygen regulates the variance of the output but not the mean for the Tor system. We further show that this oxygen-dependent variability stems from the phosphorelay. Trimethylamine-N-oxide (TMAO) is utilized by numerous bacteria as an electron acceptor for anaerobic respiration. In E. coli, expression of the proteins required for TMAO respiration is tightly regulated by a signal transduction system that is activated by TMAO. Curiously, although oxygen is the energetically preferred electron acceptor, TMAO is respired even in the presence of oxygen. Here we describe an interesting and unexpected form of regulation for this system in which oxygen produces highly variable expression of the TMAO utilization proteins across a population of cells without affecting the mean expression of these proteins. To our knowledge, this is the first reported example of a stimulus

  9. Evidence for gene-specific rather than transcription rate-dependent histone H3 exchange in yeast coding regions.

    Science.gov (United States)

    Gat-Viks, Irit; Vingron, Martin

    2009-02-01

    In eukaryotic organisms, histones are dynamically exchanged independently of DNA replication. Recent reports show that different coding regions differ in their amount of replication-independent histone H3 exchange. The current paradigm is that this histone exchange variability among coding regions is a consequence of transcription rate. Here we put forward the idea that this variability might be also modulated in a gene-specific manner independently of transcription rate. To that end, we study transcription rate-independent replication-independent coding region histone H3 exchange. We term such events relative exchange. Our genome-wide analysis shows conclusively that in yeast, relative exchange is a novel consistent feature of coding regions. Outside of replication, each coding region has a characteristic pattern of histone H3 exchange that is either higher or lower than what was expected by its RNAPII transcription rate alone. Histone H3 exchange in coding regions might be a way to add or remove certain histone modifications that are important for transcription elongation. Therefore, our results that gene-specific coding region histone H3 exchange is decoupled from transcription rate might hint at a new epigenetic mechanism of transcription regulation.

  10. Pregnancy Loss in Dairy Cattle: Relationship of Ultrasound, Blood Pregnancy-Specific Protein B, Progesterone and Production Variables.

    Science.gov (United States)

    Gábor, G; Kastelic, J P; Abonyi-Tóth, Z; Gábor, P; Endrődi, T; Balogh, O G

    2016-08-01

    Objectives were to determine associations between percentage pregnancy loss (PPL) in dairy cattle and: (i) pregnancy diagnosis by ultrasonography; (ii) pregnancy diagnosis by serum pregnancy-specific protein B (PSPB) concentrations, with or without serum progesterone concentrations; and (iii) production and environmental factors. This study included 149 822 pregnancy diagnoses conducted over 13 years in Holstein-Friesian cows in Hungarian dairy herds. The following were determined: PPL in cows diagnosed pregnant by transrectal ultrasonography 29-42 days after artificial insemination (AI; n = 11 457); PPL in cows diagnosed pregnant by serum PSPB 29-35 days after AI (n = 138 365); and PPL and its association with serum progesterone concentrations, PSPB and production/environmental variables. The definition of PPL was percentage of cows initially diagnosed pregnant based on ultrasonography or PSPB, but not pregnant when examined by transrectal palpation 60 -70 days after AI. The PPL was lower (p 1.1 ng/ml) was lowest (15.0%), whereas cows with low concentrations of both PSPB and progesterone (0.6-1.1 and production, when ambient temperatures were high, although body condition score (BCS) had no effect on PPL. Finally, there were no significant associations between serum PSPB and environmental temperatures or number of post-partum uterine treatments. © 2016 Blackwell Verlag GmbH.

  11. Specific proliferation rates of human osteoblasts on calcium phosphate surfaces with variable concentrations of α-TCP

    International Nuclear Information System (INIS)

    Santos, Euler A. dos; Farina, Marcos; Soares, Gloria A.

    2007-01-01

    Ideally, ceramics used in the repair of bone defects need to be resorbed and replaced by newly formed bone in vivo. Tricalcium phosphate (TCP) has been widely used in association with hydroxyapatite (HA) due to its higher resorption kinetics when compared with HA alone. The aim of our study was to quantitatively investigate the effect of α-tricalcium phosphate (α-TCP) on human osteoblasts' adhesion and proliferation. Ceramic samples with variable concentrations of α-TCP and HA were produced by the calcination of calcium-deficient and stoichiometric HA. Human osteoblasts were cultured on the materials in three distinct experiments with different concentrations of cells. Numerical evaluation of cellular growth along time in culture was performed for each condition. The quantity of cells seeded onto the ceramics seems to influence the osteoblast behavior once proliferation was lower when more cells were seeded onto the samples. However, a smaller content of α-TCP in relation to that of HA did not significantly modify the specific proliferation rates of the osteoblasts. Only after a long time in culture, the increasing of the α-TCP content seems to change the cells' behavior

  12. Increased Variability and Asymmetric Expansion of the Hippocampal Spatial Representation in a Distal Cue-Dependent Memory Task.

    Science.gov (United States)

    Park, Seong-Beom; Lee, Inah

    2016-08-01

    Place cells in the hippocampus fire at specific positions in space, and distal cues in the environment play critical roles in determining the spatial firing patterns of place cells. Many studies have shown that place fields are influenced by distal cues in foraging animals. However, it is largely unknown whether distal-cue-dependent changes in place fields appear in different ways in a memory task if distal cues bear direct significance to achieving goals. We investigated this possibility in this study. Rats were trained to choose different spatial positions in a radial arm in association with distal cue configurations formed by visual cue sets attached to movable curtains around the apparatus. The animals were initially trained to associate readily discernible distal cue configurations (0° vs. 80° angular separation between distal cue sets) with different food-well positions and then later experienced ambiguous cue configurations (14° and 66°) intermixed with the original cue configurations. Rats showed no difficulty in transferring the associated memory formed for the original cue configurations when similar cue configurations were presented. Place field positions remained at the same locations across different cue configurations, whereas stability and coherence of spatial firing patterns were significantly disrupted when ambiguous cue configurations were introduced. Furthermore, the spatial representation was extended backward and skewed more negatively at the population level when processing ambiguous cue configurations, compared with when processing the original cue configurations only. This effect was more salient for large cue-separation conditions than for small cue-separation conditions. No significant rate remapping was observed across distal cue configurations. These findings suggest that place cells in the hippocampus dynamically change their detailed firing characteristics in response to a modified cue environment and that some of the firing

  13. Diurnal and seasonal variability in size-dependent atmospheric deposition fluxes of polycyclic aromatic hydrocarbons in an urban center

    Science.gov (United States)

    Zhang, Kai; Zhang, Bao-Zhong; Li, Shao-Meng; Zhang, Lei-Ming; Staebler, Ralf; Zeng, Eddy Y.

    2012-09-01

    Atmospheric gaseous and size-segregated particle samples were collected from urban Guangzhou at the heights of 100 and 150 m above the ground in daytime and at night in August and December 2010, and were analyzed for polycyclic aromatic hydrocarbons (PAHs). Particulate PAHs were more abundant at night than in daytime, and significantly higher in winter than in summer. The observed vertical, diurnal, and seasonal variability in the occurrences of PAH were attributed to varying meteorological conditions and atmospheric boundary layers. More than 60% of the particulate PAHs were contained in particles in the accumulation mode with an aerodynamic diameter (Dp) in the range of 0.1-1.8 μm. Different mass transfer velocities by volatilization and condensation are considered the main causes for the different particle size distributions among individual PAHs, while combustion at different temperatures and atmospheric transport were probable causes of the observed seasonal variation in the size distribution of PAHs. Based on the modeled size-dependent dry deposition velocities, daily mean dry deposition fluxes of particulate PAHs ranged from 604 to 1190 ng m-2 d-1, with PAHs in coarse particles (Dp > 1.8 μm) accounting for 55-95% of the total fluxes. In addition, gaseous PAHs were estimated to contribute 0.6-3.1% to the total dry deposition fluxes if a conservative dry deposition velocity for gaseous species (2 × 10-4 m s-1) were used. Finally, disequilibrium phase partitioning, meteorological conditions and atmospheric transport were regarded as the main reasons for the variances in dry deposition velocities of individual PAHs.

  14. Temperature-dependent, behavioural, and transcriptional variability of a tritrophic interaction consisting of bean, herbivorous mite, and predator.

    Science.gov (United States)

    Ozawa, Rika; Nishimura, Osamu; Yazawa, Shigenobu; Muroi, Atsushi; Takabayashi, Junji; Arimura, Gen-ichiro

    2012-11-01

    Different organisms compensate for, and adapt to, environmental changes in different ways. In this way, environmental changes affect animal-plant interactions. In this study, we assessed the effect of temperature on a tritrophic system of the lima bean, the herbivorous spider mite Tetranychus urticae and the predatory mite Phytoseiulus persimilis. In this system, the plant defends itself against T. urticae by emitting volatiles that attract P. persimilis. Over 20-40 °C, the emission of volatiles by infested plants and the subsequent attraction of P. persimilis peaked at 30 °C, but the number of eggs laid by T. urticae adults and the number of eggs consumed by P. persimilis peaked at 35 °C. This indicates that the spider mites and predatory mites performed best at a higher temperature than that at which most volatile attractants were produced. Our data from transcriptome pyrosequencing of the mites found that P. persimilis up-regulated gene families for heat shock proteins (HSPs) and ubiquitin-associated proteins, whereas T. urticae did not. RNA interference-mediated gene suppression in P. persimilis revealed differences in temperature responses. Predation on T. urticae eggs by P. persimilis that had been fed PpHsp70-1 dsRNA was low at 35 °C but not at 25 °C when PpHsp70-1 expression was very high. Overall, our molecular and behavioural approaches revealed that the mode and tolerance of lima bean, T. urticae and P. persimilis are distinctly affected by temperature variability, thereby making their tritrophic interactions temperature dependent. © 2012 Blackwell Publishing Ltd.

  15. A vanadium-dependent bromoperoxidase in the marine red alga Kappaphycus alvarezii (Doty) Doty displays clear substrate specificity.

    Science.gov (United States)

    Kamenarska, Zornitsa; Taniguchi, Tomokazu; Ohsawa, Noboru; Hiraoka, Masanori; Itoh, Nobuya

    2007-05-01

    Bromoperoxidase activity was initially detected in marine macroalgae belonging to the Solieriaceae family (Gigartinales, Rhodophyta), including Solieria robusta (Greville) Kylin, Eucheuma serra J. Agardh and Kappaphycus alvarezii (Doty) Doty, which are important industrial sources of the polysaccharide carrageenan. Notably, the purification of bromoperoxidase was difficult because due to the coexistence of viscoid polysaccharides. The activity of the partially purified enzyme was dependent on the vanadate ion, and displayed a distinct substrate spectrum from that of previously reported vanadium-dependent bromoperoxidases of marine macroalgae. The enzyme was specific for Br- and I- ions and inactive toward F- and Cl-. The K(m) values for Br- and H2O2 were 2.5x10(-3) M and 8.5x10(-5) M, respectively. The halogenated product, dibromoacetaldehyde, that accumulated in K. alvarezii was additionally determined.

  16. Specific gravity of hybrid poplars in the north-central region, USA: within-tree variability and site × genotype effects

    Science.gov (United States)

    William L. Headlee; Ronald S. Jr. Zalesny; Richard B. Hall; Edmund O. Bauer; Bradford Bender; Bruce A. Birr; Raymond O. Miller; Jesse A. Randall; Adam H. Wiese

    2013-01-01

    Specific gravity is an important consideration for traditional uses of hybrid poplars for pulp and solid wood products, as well as for biofuels and bioenergy production. While specific gravity has been shown to be under strong genetic control and subject to within-tree variability, the role of genotype × environment interactions is poorly understood. Most...

  17. Model for the orientation, magnetic field, and temperature dependence of the specific heat of CeCu6

    International Nuclear Information System (INIS)

    Edelstein, A.S.

    1988-01-01

    The results of a model calculation of the orientation, magnetic field, and temperature dependence of the specific heat C of CeCu 6 are found to be in good agreement with the single-crystal data of Amato et al. The model incorporates both the Kondo and crystal-field effects. It is suggested that the low-temperature Wilson's ratio CTchi, where chi is the susceptibility, may not change in an applied field H and that both CT and chi at low temperatures as a function of H may be proportional to the many-body density of states at the energy μH

  18. Specific Oral Tolerance Induction Using IFN-Gamma in 2 Cases of Food-Dependent Exercise-Induced Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Geunwoong Noh

    2013-01-01

    Full Text Available Anaphylaxis induced by exercise after the intake of certain foods is referred to as food-dependent exercise-induced anaphylaxis (FDEIA. Only the preventive medication such as oral sodium cromoglycate and oral combined cetirizine-montelukast was tried in FDEIA. Specific oral tolerance induction (SOTI using IFN-gamma was tried in 2 cases of FDEIA for wheat. Merely, exercise accompanied every treatment just after the intake of allergenic foods during treatment. Patients acquired tolerance for wheat in both cases successfully. After treatment, two patients take wheat in their food living freely. Conclusively, SOTI using IFN-gamma was effective as the causative treatment for allergenic foods in FDEIA.

  19. Stage-specific and age-dependent profiles of zinc, copper, manganese, and selenium in rat seminiferous tubules

    International Nuclear Information System (INIS)

    Homma-Takeda, S.; Nishimura, Y.; Watanabe, Y.; Imaseki, H.; Yukawa, M.

    2004-01-01

    Stage-specific and age-dependent profiles of zinc, copper, manganese, and selenium in testis were examined in Wistar rats by both inductively coupled argon plasma-mass spectrometry (ICP-MS) with a microdissection technique and in situ elemental imaging of micro-PIXE analysis. The young adult animals (10 weeks old) contained higher levels of zinc and manganese in the seminiferous tubules at stages VII-VIII than stages XI through VI and IX-X and the levels were higher than those of the immature and old animals. Copper and selenium levels at stages VII-VIII of the young adult animals were also higher than those of the immature and old animals. In stages VII and VIII, zinc was higher in the central area of the seminiferous epithelium, where spermatozoa were localized, demonstrating a cell-specific property. (author)

  20. Impact parameter dependence of the specific entropy and the light particle yield in relativistic heavy ion collisions

    International Nuclear Information System (INIS)

    Gudima, K.K.; Toneev, V.D.

    1986-01-01

    The connection between the fragment yield and the associated specific entropy of particles produced in the course of a relativistic heavy ion collision is studied within the cascade approach. The essential impact parameter dependence of the fragment yield indicates that the specific entropy increases with impact parameter and that the critical density of the system decay is the larger the more central the collision process is. The results show that the thermodynamical equilibrium limit for the entropy production is not reached for such heavy systems as Nb+Nb at 400 MeV/nucleon and that the finite size effects and the dynamical freeze-out process are dominant factors in determining the cluster yield

  1. Reconstructed ancestral enzymes reveal that negative selection drove the evolution of substrate specificity in ADP-dependent kinases.

    Science.gov (United States)

    Castro-Fernandez, Víctor; Herrera-Morande, Alejandra; Zamora, Ricardo; Merino, Felipe; Gonzalez-Ordenes, Felipe; Padilla-Salinas, Felipe; Pereira, Humberto M; Brandão-Neto, Jose; Garratt, Richard C; Guixe, Victoria

    2017-09-22

    One central goal in molecular evolution is to pinpoint the mechanisms and evolutionary forces that cause an enzyme to change its substrate specificity; however, these processes remain largely unexplored. Using the glycolytic ADP-dependent kinases of archaea, including the orders Thermococcales , Methanosarcinales , and Methanococcales , as a model and employing an approach involving paleoenzymology, evolutionary statistics, and protein structural analysis, we could track changes in substrate specificity during ADP-dependent kinase evolution along with the structural determinants of these changes. To do so, we studied five key resurrected ancestral enzymes as well as their extant counterparts. We found that a major shift in function from a bifunctional ancestor that could phosphorylate either glucose or fructose 6-phosphate (fructose-6-P) as a substrate to a fructose 6-P-specific enzyme was started by a single amino acid substitution resulting in negative selection with a ground-state mode against glucose and a subsequent 1,600-fold change in specificity of the ancestral protein. This change rendered the residual phosphorylation of glucose a promiscuous and physiologically irrelevant activity, highlighting how promiscuity may be an evolutionary vestige of ancestral enzyme activities, which have been eliminated over time. We also could reconstruct the evolutionary history of substrate utilization by using an evolutionary model of discrete binary characters, indicating that substrate uses can be discretely lost or acquired during enzyme evolution. These findings exemplify how negative selection and subtle enzyme changes can lead to major evolutionary shifts in function, which can subsequently generate important adaptive advantages, for example, in improving glycolytic efficiency in Thermococcales . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Increased CEST specificity for amide and fast-exchanging amine protons using exchange-dependent relaxation rate.

    Science.gov (United States)

    Zhang, Xiao-Yong; Wang, Feng; Xu, Junzhong; Gochberg, Daniel F; Gore, John C; Zu, Zhongliang

    2018-02-01

    Chemical exchange saturation transfer (CEST) imaging of amides at 3.5 ppm and fast-exchanging amines at 3 ppm provides a unique means to enhance the sensitivity of detection of, for example, proteins/peptides and neurotransmitters, respectively, and hence can provide important information on molecular composition. However, despite the high sensitivity relative to conventional magnetic resonance spectroscopy (MRS), in practice, CEST often has relatively poor specificity. For example, CEST signals are typically influenced by several confounding effects, including direct water saturation (DS), semi-solid non-specific magnetization transfer (MT), the influence of water relaxation times (T 1w ) and nearby overlapping CEST signals. Although several editing techniques have been developed to increase the specificity by removing DS, semi-solid MT and T 1w influences, it is still challenging to remove overlapping CEST signals from different exchanging sites. For instance, the amide proton transfer (APT) signal could be contaminated by CEST effects from fast-exchanging amines at 3 ppm and intermediate-exchanging amines at 2 ppm. The current work applies an exchange-dependent relaxation rate (R ex ) to address this problem. Simulations demonstrate that: (1) slowly exchanging amides and fast-exchanging amines have distinct dependences on irradiation powers; and (2) R ex serves as a resonance frequency high-pass filter to selectively reduce CEST signals with resonance frequencies closer to water. These characteristics of R ex provide a means to isolate the APT signal from amines. In addition, previous studies have shown that CEST signals from fast-exchanging amines have no distinct features around their resonance frequencies. However, R ex gives Lorentzian lineshapes centered at their resonance frequencies for fast-exchanging amines and thus can significantly increase the specificity of CEST imaging for amides and fast-exchanging amines. Copyright © 2017 John Wiley & Sons

  3. A Xylenol Orange-Based Screening Assay for the Substrate Specificity of Flavin-Dependent para-Phenol Oxidases

    Directory of Open Access Journals (Sweden)

    Tom A. Ewing

    2018-01-01

    Full Text Available Vanillyl alcohol oxidase (VAO and eugenol oxidase (EUGO are flavin-dependent enzymes that catalyse the oxidation of para-substituted phenols. This makes them potentially interesting biocatalysts for the conversion of lignin-derived aromatic monomers to value-added compounds. To facilitate their biocatalytic exploitation, it is important to develop methods by which variants of the enzymes can be rapidly screened for increased activity towards substrates of interest. Here, we present the development of a screening assay for the substrate specificity of para-phenol oxidases based on the detection of hydrogen peroxide using the ferric-xylenol orange complex method. The assay was used to screen the activity of VAO and EUGO towards a set of twenty-four potential substrates. This led to the identification of 4-cyclopentylphenol as a new substrate of VAO and EUGO and 4-cyclohexylphenol as a new substrate of VAO. Screening of a small library of VAO and EUGO active-site variants for alterations in their substrate specificity led to the identification of a VAO variant (T457Q with increased activity towards vanillyl alcohol (4-hydroxy-3-methoxybenzyl alcohol and a EUGO variant (V436I with increased activity towards chavicol (4-allylphenol and 4-cyclopentylphenol. This assay provides a quick and efficient method to screen the substrate specificity of para-phenol oxidases, facilitating the enzyme engineering of known para-phenol oxidases and the evaluation of the substrate specificity of novel para-phenol oxidases.

  4. A Xylenol Orange-Based Screening Assay for the Substrate Specificity of Flavin-Dependent para-Phenol Oxidases.

    Science.gov (United States)

    Ewing, Tom A; van Noord, Aster; Paul, Caroline E; van Berkel, Willem J H

    2018-01-14

    Vanillyl alcohol oxidase (VAO) and eugenol oxidase (EUGO) are flavin-dependent enzymes that catalyse the oxidation of para -substituted phenols. This makes them potentially interesting biocatalysts for the conversion of lignin-derived aromatic monomers to value-added compounds. To facilitate their biocatalytic exploitation, it is important to develop methods by which variants of the enzymes can be rapidly screened for increased activity towards substrates of interest. Here, we present the development of a screening assay for the substrate specificity of para -phenol oxidases based on the detection of hydrogen peroxide using the ferric-xylenol orange complex method. The assay was used to screen the activity of VAO and EUGO towards a set of twenty-four potential substrates. This led to the identification of 4-cyclopentylphenol as a new substrate of VAO and EUGO and 4-cyclohexylphenol as a new substrate of VAO. Screening of a small library of VAO and EUGO active-site variants for alterations in their substrate specificity led to the identification of a VAO variant (T457Q) with increased activity towards vanillyl alcohol (4-hydroxy-3-methoxybenzyl alcohol) and a EUGO variant (V436I) with increased activity towards chavicol (4-allylphenol) and 4-cyclopentylphenol. This assay provides a quick and efficient method to screen the substrate specificity of para -phenol oxidases, facilitating the enzyme engineering of known para- phenol oxidases and the evaluation of the substrate specificity of novel para -phenol oxidases.

  5. A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling.

    Science.gov (United States)

    Lin, Hong-Yu; Haegele, Joseph A; Disare, Michael T; Lin, Qishan; Aye, Yimon

    2015-05-20

    Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.

  6. An Analysis of Some Variables Affecting the Internet Dependency Level of Turkish Adolescents by Using Decision Tree Methods

    Science.gov (United States)

    Kayri, Murat; Gunuc, Selim

    2010-01-01

    Internet dependency is going to expand into social life in wide area whereas it has been accepted as a pathological and psychological disease. Knowing the basic effects of internet dependency is an inevitable approach to use the internet technology healthy. In this study, internet dependency levels of 754 students were examined with the Internet…

  7. Ploidy-dependent changes in the epigenome of symbiotic cells correlate with specific patterns of gene expression

    KAUST Repository

    Nagymihály, Marianna

    2017-04-13

    The formation of symbiotic nodule cells in Medicago truncatula is driven by successive endoreduplication cycles and transcriptional reprogramming in different temporal waves including the activation of more than 600 cysteine-rich NCR genes expressed only in nodules. We show here that the transcriptional waves correlate with growing ploidy levels and have investigated how the epigenome changes during endoreduplication cycles. Differential DNA methylation was found in only a small subset of symbiotic nodule-specific genes, including more than half of the NCR genes, whereas in most genes DNA methylation was unaffected by the ploidy levels and was independent of the genes\\' active or repressed state. On the other hand, expression of nodule-specific genes correlated with ploidy-dependent opening of the chromatin as well as, in a subset of tested genes, with reduced H3K27me3 levels combined with enhanced H3K9ac levels. Our results suggest that endoreduplication-dependent epigenetic changes contribute to transcriptional reprogramming in the differentiation of symbiotic cells.

  8. Specific absorption rate dependence on temperature in magnetic field hyperthermia measured by dynamic hysteresis losses (ac magnetometry)

    Science.gov (United States)

    Garaio, Eneko; Sandre, Olivier; Collantes, Juan-Mari; Garcia, Jose Angel; Mornet, Stéphane; Plazaola, Fernando

    2015-01-01

    Magnetic nanoparticles (NPs) are intensively studied for their potential use for magnetic hyperthermia, a treatment that has passed a phase II clinical trial against severe brain cancer (glioblastoma) at the end of 2011. Their heating power, characterized by the ‘specific absorption rate (SAR)’, is often considered temperature independent in the literature, mainly because of the difficulties that arise from the measurement methodology. Using a dynamic magnetometer presented in a recent paper, we measure here the thermal dependence of SAR for superparamagnetic iron oxide (maghemite) NPs of four different size-ranges corresponding to mean diameters around 12 nm, 14 nm, 15 nm and 16 nm. The article reports a parametrical study extending from 10 to 60 {}^\\circ C in temperature, from 75 to 1031 kHz in frequency, and from 2 to 24 kA m-1 in magnetic field strength. It was observed that SAR values of smaller NPs decrease with temperature whereas for the larger sample (16 nm) SAR values increase with temperature. The measured variation of SAR with temperature is frequency dependent. This behaviour is fully explained within the scope of linear response theory based on Néel and Brown relaxation processes, using independent magnetic measurements of the specific magnetization and the magnetic anisotropy constant. A good quantitative agreement between experimental values and theoretical values is confirmed in a tri-dimensional space that uses as coordinates the field strength, the frequency and the temperature.

  9. Signal or noise? Separating grain size-dependent Nd isotope variability from provenance shifts in Indus delta sediments, Pakistan

    Science.gov (United States)

    Jonell, T. N.; Li, Y.; Blusztajn, J.; Giosan, L.; Clift, P. D.

    2017-12-01

    Rare earth element (REE) radioisotope systems, such as neodymium (Nd), have been traditionally used as powerful tracers of source provenance, chemical weathering intensity, and sedimentary processes over geologic timescales. More recently, the effects of physical fractionation (hydraulic sorting) of sediments during transport have called into question the utility of Nd isotopes as a provenance tool. Is source terrane Nd provenance resolvable if sediment transport strongly induces noise? Can grain-size sorting effects be quantified? This study works to address such questions by utilizing grain size analysis, trace element geochemistry, and Nd isotope geochemistry of bulk and grain-size fractions (Pakistan. Here we evaluate how grain size effects drive Nd isotope variability and further resolve the total uncertainties associated with Nd isotope compositions of bulk sediments. Results from the Indus delta indicate bulk sediment ɛNd compositions are most similar to the <63 µm fraction as a result of strong mineralogical control on bulk compositions by silt- to clay-sized monazite and/or allanite. Replicate analyses determine that the best reproducibility (± 0.15 ɛNd points) is observed in the 125-250 µm fraction. The bulk and finest fractions display the worst reproducibility (±0.3 ɛNd points). Standard deviations (2σ) indicate that bulk sediment uncertainties are no more than ±1.0 ɛNd points. This argues that excursions of ≥1.0 ɛNd points in any bulk Indus delta sediments must in part reflect an external shift in provenance irrespective of sample composition, grain size, and grain size distribution. Sample standard deviations (2s) estimate that any terrigenous bulk sediment composition should vary no greater than ±1.1 ɛNd points if provenance remains constant. Findings from this study indicate that although there are grain-size dependent Nd isotope effects, they are minimal in the Indus delta such that resolvable provenance-driven trends can be

  10. Calcium-Dependent Protein Kinases from Arabidopsis show substrate specificity differences in an analysis of 103 substrates

    Directory of Open Access Journals (Sweden)

    Amy eCurran

    2011-08-01

    Full Text Available The identification of substrates represents a critical challenge for understanding any protein kinase-based signal transduction pathway. In Arabidopsis, there are more than 1000 different protein kinases, 34 of which belong to a family of Ca2+-dependent protein kinases (CPKs. While CPKs are implicated in regulating diverse aspects of plant biology, from ion transport to transcription, relatively little is known about isoform-specific differences in substrate specificity, or the number of phosphorylation targets. Here, in vitro kinase assays were used to compare phosphorylation targets of four CPKs from Arabidopsis (CPK1, 10, 16 and 34. Significant differences in substrate specificity for each kinase were revealed by assays using 103 different substrates. For example CPK16 phosphorylated Serine 109 in a peptide from the stress-regulated protein, Di19-2 with KM ~70 µM, but this site was not phosphorylated significantly by CPKs 1, 10, or 34. In contrast, CPKs 1, 10, and 34 phosphorylated 93 other peptide substrates not recognized by CPK16. Examples of substrate specificity differences among all four CPKs were verified by kinetic analyses. To test the correlation between in vivo phosphorylation events and in vitro kinase activities, assays were performed with 274 synthetic peptides that contained phosphorylation sites previously mapped in proteins isolated from plants (in vivo-mapped sites. Of these, 74 (27% were found to be phosphorylated by at least one of the four CPKs tested. This 27% success rate validates a robust strategy for linking the activities of specific kinases, such as CPKs, to the thousands of in planta phosphorylation sites that are being uncovered by emerging technologies.

  11. TLR2-dependent inhibition of macrophage responses to IFN-gamma is mediated by distinct, gene-specific mechanisms.

    Directory of Open Access Journals (Sweden)

    Sarah A Benson

    2009-07-01

    Full Text Available Mycobacterium tuberculosis uses multiple mechanisms to avoid elimination by the immune system. We have previously shown that M. tuberculosis can inhibit selected macrophage responses to IFN-gamma through TLR2-dependent and -independent mechanisms. To specifically address the role of TLR2 signaling in mediating this inhibition, we stimulated macrophages with the specific TLR2/1 ligand Pam(3CSK(4 and assayed responses to IFN-gamma. Pam(3CSK(4 stimulation prior to IFN-gamma inhibited transcription of the unrelated IFN-gamma-inducible genes, CIITA and CXCL11. Surface expression of MHC class II and secretion of CXCL11 were greatly reduced as well, indicating that the reduction in transcripts had downstream effects. Inhibition of both genes required new protein synthesis. Using chromatin immunoprecipitation, we found that TLR2 stimulation inhibited IFN-gamma-induced RNA polymerase II binding to the CIITA and CXCL11 promoters. Furthermore, TATA binding protein was unable to bind the TATA box of the CXCL11 promoter, suggesting that assembly of transcriptional machinery was disrupted. However, TLR2 stimulation affected chromatin modifications differently at each of the inhibited promoters. Histone H3 and H4 acetylation was reduced at the CIITA promoter but unaffected at the CXCL11 promoter. In addition, NF-kappaB signaling was required for inhibition of CXCL11 transcription, but not for inhibition of CIITA. Taken together, these results indicate that TLR2-dependent inhibition of IFN-gamma-induced gene expression is mediated by distinct, gene-specific mechanisms that disrupt binding of the transcriptional machinery to the promoters.

  12. Convergence Analysis of Semi-Implicit Euler Methods for Solving Stochastic Age-Dependent Capital System with Variable Delays and Random Jump Magnitudes

    Directory of Open Access Journals (Sweden)

    Qinghui Du

    2014-01-01

    Full Text Available We consider semi-implicit Euler methods for stochastic age-dependent capital system with variable delays and random jump magnitudes, and investigate the convergence of the numerical approximation. It is proved that the numerical approximate solutions converge to the analytical solutions in the mean-square sense under given conditions.

  13. SU-C-304-07: Are Small Field Detector Correction Factors Strongly Dependent On Machine-Specific Characteristics?

    International Nuclear Information System (INIS)

    Mathew, D; Tanny, S; Parsai, E; Sperling, N

    2015-01-01

    Purpose: The current small field dosimetry formalism utilizes quality correction factors to compensate for the difference in detector response relative to dose deposited in water. The correction factors are defined on a machine-specific basis for each beam quality and detector combination. Some research has suggested that the correction factors may only be weakly dependent on machine-to-machine variations, allowing for determinations of class-specific correction factors for various accelerator models. This research examines the differences in small field correction factors for three detectors across two Varian Truebeam accelerators to determine the correction factor dependence on machine-specific characteristics. Methods: Output factors were measured on two Varian Truebeam accelerators for equivalently tuned 6 MV and 6 FFF beams. Measurements were obtained using a commercial plastic scintillation detector (PSD), two ion chambers, and a diode detector. Measurements were made at a depth of 10 cm with an SSD of 100 cm for jaw-defined field sizes ranging from 3×3 cm 2 to 0.6×0.6 cm 2 , normalized to values at 5×5cm 2 . Correction factors for each field on each machine were calculated as the ratio of the detector response to the PSD response. Percent change of correction factors for the chambers are presented relative to the primary machine. Results: The Exradin A26 demonstrates a difference of 9% for 6×6mm 2 fields in both the 6FFF and 6MV beams. The A16 chamber demonstrates a 5%, and 3% difference in 6FFF and 6MV fields at the same field size respectively. The Edge diode exhibits less than 1.5% difference across both evaluated energies. Field sizes larger than 1.4×1.4cm2 demonstrated less than 1% difference for all detectors. Conclusion: Preliminary results suggest that class-specific correction may not be appropriate for micro-ionization chamber. For diode systems, the correction factor was substantially similar and may be useful for class-specific reference

  14. SU-C-304-07: Are Small Field Detector Correction Factors Strongly Dependent On Machine-Specific Characteristics?

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, D; Tanny, S; Parsai, E; Sperling, N [University of Toledo Medical Center, Toledo, OH (United States)

    2015-06-15

    Purpose: The current small field dosimetry formalism utilizes quality correction factors to compensate for the difference in detector response relative to dose deposited in water. The correction factors are defined on a machine-specific basis for each beam quality and detector combination. Some research has suggested that the correction factors may only be weakly dependent on machine-to-machine variations, allowing for determinations of class-specific correction factors for various accelerator models. This research examines the differences in small field correction factors for three detectors across two Varian Truebeam accelerators to determine the correction factor dependence on machine-specific characteristics. Methods: Output factors were measured on two Varian Truebeam accelerators for equivalently tuned 6 MV and 6 FFF beams. Measurements were obtained using a commercial plastic scintillation detector (PSD), two ion chambers, and a diode detector. Measurements were made at a depth of 10 cm with an SSD of 100 cm for jaw-defined field sizes ranging from 3×3 cm{sup 2} to 0.6×0.6 cm{sup 2}, normalized to values at 5×5cm{sup 2}. Correction factors for each field on each machine were calculated as the ratio of the detector response to the PSD response. Percent change of correction factors for the chambers are presented relative to the primary machine. Results: The Exradin A26 demonstrates a difference of 9% for 6×6mm{sup 2} fields in both the 6FFF and 6MV beams. The A16 chamber demonstrates a 5%, and 3% difference in 6FFF and 6MV fields at the same field size respectively. The Edge diode exhibits less than 1.5% difference across both evaluated energies. Field sizes larger than 1.4×1.4cm2 demonstrated less than 1% difference for all detectors. Conclusion: Preliminary results suggest that class-specific correction may not be appropriate for micro-ionization chamber. For diode systems, the correction factor was substantially similar and may be useful for class-specific

  15. Domain-specific perceptual causality in children depends on the spatio-temporal configuration, not motion onset

    Directory of Open Access Journals (Sweden)

    Anne eSchlottmann

    2013-07-01

    Full Text Available Humans, even babies, perceive causality when one shape moves briefly and linearly after another. Motion timing is crucial in this and causal impressions disappear with short delays between motions. However, the role of temporal information is more complex: It is both a cue to causality and a factor that constrains processing. It affects ability to distinguish causality from non-causality, and social from mechanical causality. Here we study both issues with 3- to 7-year-olds and adults who saw two computer-animated squares and chose if a picture of mechanical, social or non-causality fit each event best. Prior work fit with the standard view that early in development, the distinction between the social and physical domains depends mainly on whether or not the agents make contact, and that this reflects concern with domain-specific motion onset, in particular, whether the motion is self-initiated or not. The present experiments challenge both parts of this position. In Experiments 1 and 2, we showed that not just spatial, but also animacy and temporal information affect how children distinguish between physical and social causality. In Experiments 3 and 4 we showed that children do not seem to use spatio-temporal information in perceptual causality to make inferences about self- or other-initiated motion onset. Overall, spatial contact may be developmentally primary in domain-specific perceptual causality in that it is processed easily and is dominant over competing cues, but it is not the only cue used early on and it is not used to infer motion onset. Instead, domain-specific causal impressions may be automatic reactions to specific perceptual configurations, with a complex role for temporal information.

  16. Density-dependent sex ratio and sex-specific preference for host traits in parasitic bat flies.

    Science.gov (United States)

    Szentiványi, Tamara; Vincze, Orsolya; Estók, Péter

    2017-08-29

    Deviation of sex ratios from unity in wild animal populations has recently been demonstrated to be far more prevalent than previously thought. Ectoparasites are prominent examples of this bias, given that their sex ratios vary from strongly female- to strongly male-biased both among hosts and at the metapopulation level. To date our knowledge is very limited on how and why these biased sex ratios develop. It was suggested that sex ratio and sex-specific aggregation of ectoparasites might be shaped by the ecology, behaviour and physiology of both hosts and their parasites. Here we investigate a highly specialised, hematophagous bat fly species with strong potential to move between hosts, arguably limited inbreeding effects, off-host developmental stages and extended parental care. We collected a total of 796 Nycteribia kolenatii bat flies from 147 individual bats using fumigation and subsequently determined their sex. We report a balanced sex ratio at the metapopulation level and a highly variable sex ratio among infrapopulations ranging from 100% male to 100% female. We show that infrapopulation sex ratio is not random and is highly correlated with infrapopulation size. Sex ratio is highly male biased in small and highly female biased in large infrapopulations. We show that this pattern is most probably the result of sex-specific preference in bat flies for host traits, most likely combined with a higher mobility of males. We demonstrate that female bat flies exert a strong preference for high host body condition and female hosts, while the distribution of males is more even. Our results suggest that locally biased sex ratios can develop due to sex-specific habitat preference of parasites. Moreover, it is apparent that the sex of both hosts and parasites need to be accounted for when a better understanding of host-parasite systems is targeted.

  17. On the nature and nurture of intelligence and specific cognitive abilities: the more heritable, the more culture dependent.

    Science.gov (United States)

    Kan, Kees-Jan; Wicherts, Jelte M; Dolan, Conor V; van der Maas, Han L J

    2013-12-01

    To further knowledge concerning the nature and nurture of intelligence, we scrutinized how heritability coefficients vary across specific cognitive abilities both theoretically and empirically. Data from 23 twin studies (combined N = 7,852) showed that (a) in adult samples, culture-loaded subtests tend to demonstrate greater heritability coefficients than do culture-reduced subtests; and (b) in samples of both adults and children, a subtest's proportion of variance shared with general intelligence is a function of its cultural load. These findings require an explanation because they do not follow from mainstream theories of intelligence. The findings are consistent with our hypothesis that heritability coefficients differ across cognitive abilities as a result of differences in the contribution of genotype-environment covariance. The counterintuitive finding that the most heritable abilities are the most culture-dependent abilities sheds a new light on the long-standing nature-nurture debate of intelligence.

  18. Electronic Excitations in Solution: The Interplay between State Specific Approaches and a Time-Dependent Density Functional Theory Description.

    Science.gov (United States)

    Guido, Ciro A; Jacquemin, Denis; Adamo, Carlo; Mennucci, Benedetta

    2015-12-08

    We critically analyze the performances of continuum solvation models when coupled to time-dependent density functional theory (TD-DFT) to predict solvent effects on both absorption and emission energies of chromophores in solution. Different polarization schemes of the polarizable continuum model (PCM), such as linear response (LR) and three different state specific (SS) approaches, are considered and compared. We show the necessity of introducing a SS model in cases where large electron density rearrangements are involved in the excitations, such as charge-transfer transitions in both twisted and quadrupolar compounds, and underline the very delicate interplay between the selected polarization method and the chosen exchange-correlation functional. This interplay originates in the different descriptions of the transition and ground/excited state multipolar moments by the different functionals. As a result, the choice of both the DFT functional and the solvent polarization scheme has to be consistent with the nature of the studied electronic excitation.

  19. Vaccine induced antibodies to the first variable loop of human immunodeficiency virus type 1 gp120, mediate antibody-dependent virus inhibition in macaques.

    Science.gov (United States)

    Bialuk, Izabela; Whitney, Stephen; Andresen, Vibeke; Florese, Ruth H; Nacsa, Janos; Cecchinato, Valentina; Valeri, Valerio W; Heraud, Jean-Michel; Gordon, Shari; Parks, Robyn Washington; Montefiori, David C; Venzon, David; Demberg, Thorsten; Guroff, Marjorie Robert-; Landucci, Gary; Forthal, Donald N; Franchini, Genoveffa

    2011-12-09

    The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region of gp120 is associated with control of highly pathogenic chimeric SHIV(89.6P) replication in rhesus macaques. The vaccinated animal that had the highest titers of antibodies to the amino terminus portion of V1, prior to challenge, had secondary antibody responses that mediated cell killing by antibody-dependent cellular cytotoxicity (ADCC), as early as 2 weeks after infection and inhibited viral replication by antibody-dependent cell-mediated virus inhibition (ADCVI), by 4 weeks after infection. There was a significant inverse correlation between virus level and binding antibody titers to the envelope protein, (R=-0.83, p=0.015), and ADCVI (R=-0.84 p=0.044). Genotyping of plasma virus demonstrated in vivo selection of three SHIV(89.6P) variants with changes in potential N-linked glycosylation sites in V1. We found a significant inverse correlation between virus levels and titers of antibodies that mediated ADCVI against all the identified V1 virus variants. A significant inverse correlation was also found between neutralizing antibody titers to SHIV(89.6) and virus levels (R=-0.72 p=0.0050). However, passive inoculation of purified immunoglobulin from animal M316, the macaque that best controlled virus, to a naïve macaque, resulted in a low serum neutralizing antibodies and low ADCVI activity that failed to protect from SHIV(89.6P) challenge. Collectively, while our data suggest that anti-envelope antibodies with neutralizing and non-neutralizing Fc(R-dependent activities may be important in the control of SHIV replication, they also demonstrate that low levels of these antibodies alone are not sufficient to protect from infection. Published by Elsevier Ltd.

  20. Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme.

    Science.gov (United States)

    Ariza, Antonio; Vickers, Tim J; Greig, Neil; Armour, Kirsten A; Dixon, Mark J; Eggleston, Ian M; Fairlamb, Alan H; Bond, Charles S

    2006-02-01

    Trypanothione replaces glutathione in defence against cellular damage caused by oxidants, xenobiotics and methylglyoxal in the trypanosomatid parasites, which cause trypanosomiasis and leishmaniasis. In Leishmania major, the first step in methylglyoxal detoxification is performed by a trypanothione-dependent glyoxalase I (GLO1) containing a nickel cofactor; all other characterized eukaryotic glyoxalases use zinc. In kinetic studies L. major and human enzymes were active with methylglyoxal derivatives of several thiols, but showed opposite substrate selectivities: N1-glutathionylspermidine hemithioacetal is 40-fold better with L. major GLO1, whereas glutathione hemithioacetal is 300-fold better with human GLO1. Similarly, S-4-bromobenzylglutathionylspermidine is a 24-fold more potent linear competitive inhibitor of L. major than human GLO1 (Kis of 0.54 microM and 12.6 microM, respectively), whereas S-4-bromobenzylglutathione is >4000-fold more active against human than L. major GLO1 (Kis of 0.13 microM and >500 microM respectively). The crystal structure of L. major GLO1 reveals differences in active site architecture to both human GLO1 and the nickel-dependent Escherichia coli GLO1, including increased negative charge and hydrophobic character and truncation of a loop that may regulate catalysis in the human enzyme. These differences correlate with the differential binding of glutathione and trypanothione-based substrates, and thus offer a route to the rational design of L. major-specific GLO1 inhibitors.

  1. Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

    Directory of Open Access Journals (Sweden)

    Shih-pi Ku

    2017-07-01

    Full Text Available The subiculum and the lateral entorhinal cortex (LEC are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1 receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum, both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors. This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval.

  2. Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex.

    Science.gov (United States)

    Ku, Shih-Pi; Nakamura, Nozomu H; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M

    2017-01-01

    The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc , which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval.

  3. Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

    Science.gov (United States)

    Ku, Shih-pi; Nakamura, Nozomu H.; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M.

    2017-01-01

    The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval. PMID:28790897

  4. Time dependent analysis of assay comparability: a novel approach to understand intra- and inter-site variability over time

    Science.gov (United States)

    Winiwarter, Susanne; Middleton, Brian; Jones, Barry; Courtney, Paul; Lindmark, Bo; Page, Ken M.; Clark, Alan; Landqvist, Claire

    2015-09-01

    We demonstrate here a novel use of statistical tools to study intra- and inter-site assay variability of five early drug metabolism and pharmacokinetics in vitro assays over time. Firstly, a tool for process control is presented. It shows the overall assay variability but allows also the following of changes due to assay adjustments and can additionally highlight other, potentially unexpected variations. Secondly, we define the minimum discriminatory difference/ratio to support projects to understand how experimental values measured at different sites at a given time can be compared. Such discriminatory values are calculated for 3 month periods and followed over time for each assay. Again assay modifications, especially assay harmonization efforts, can be noted. Both the process control tool and the variability estimates are based on the results of control compounds tested every time an assay is run. Variability estimates for a limited set of project compounds were computed as well and found to be comparable. This analysis reinforces the need to consider assay variability in decision making, compound ranking and in silico modeling.

  5. Time dependence of the UV resonance lines in the cataclysmic variables SU UMa, RX And and 0623+71

    International Nuclear Information System (INIS)

    Woods, J.A.; Drew, J.E.; Verbunt, Frank

    1990-01-01

    We present IUE observations of the dwarf novae SU UMa and RX And, and of the nova-like variable 0623 + 71. At the time of observation, SU UMa and RX And were in outburst. All three systems show variability in the wind-formed UV resonance lines of N v λ 1240, Si IV λ 1397 and C IV λ 1549 on timescale of hours. The amplitude of variation is smallest in RX And and largest in 0623 + 71. There is evidence that the variations observed in SU UMa's UV spectrum repeat on the orbital period. Our observations of SU UMa also reveal variability in the continuum flux during the decline from outburst maximum that is much more marked in the UV than at optical wavelengths. (author)

  6. CYLD, a deubiquitinase specific for lysine63-linked polyubiquitins, accumulates at the postsynaptic density in an activity-dependent manner

    International Nuclear Information System (INIS)

    Dosemeci, Ayse; Thein, Soe; Yang, Yijung; Reese, Thomas S.; Tao-Cheng, Jung-Hwa

    2013-01-01

    Highlights: ► CYLD is a deubiquitinase specific for lysine63-linked polyubiquitins. ► Presence of CYLD in PSDs is established by biochemistry and immunoEM. ► CYLD accumulates on PSDs upon depolarization of neurons. ► Accumulation of CYLD at PSDs may regulate trafficking/degradation of synaptic proteins. -- Abstract: Polyubiquitin chains on proteins flag them for distinct fates depending on the type of polyubiquitin linkage. While lysine48-linked polyubiquitination directs proteins to proteasomal degradation, lysine63-linked polyubiquitination promotes different protein trafficking and is involved in autophagy. Here we show that postsynaptic density (PSD) fractions from adult rat brain contain deubiquitinase activity that targets both lysine48 and lysine63-linked polyubiquitins. Comparison of PSD fractions with parent subcellular fractions by Western immunoblotting reveals that CYLD, a deubiquitinase specific for lysine63-linked polyubiquitins, is highly enriched in the PSD fraction. Electron microscopic examination of hippocampal neurons in culture under basal conditions shows immunogold label for CYLD at the PSD complex in approximately one in four synapses. Following depolarization by exposure to high K+, the proportion of CYLD-labeled PSDs as well as the labeling intensity of CYLD at the PSD increased by more than eighty percent, indicating that neuronal activity promotes accumulation of CYLD at the PSD. An increase in postsynaptic CYLD following activity would promote removal of lysine63-polyubiquitins from PSD proteins and thus could regulate their trafficking and prevent their autophagic degradation.

  7. Different patterns in the prognostic value of age for bladder cancer-specific survival depending on tumor stages.

    Science.gov (United States)

    Feng, Huan; Zhang, Wei; Li, Jiajun; Lu, Xiaozhe

    2015-01-01

    To compare the pathological features and long-term survival of bladder cancer (BCa) in young patients with elderly counterparts. Using the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 93115 patients with non-metastatic bladder cancer diagnosed between 1988 and 2003. Patients were categorized into young (50 years and under) and elderly groups (over 50 years of age). The overall and five-year bladder cancer specific survival (BCSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors. There were significant differences between the two groups in primary site, pathologic grading, histologic type, AJCC stage (pstage patients. The study findings show different patterns in the prognostic value of age for determining BCSS, depending on the tumor stages. Compared with elderly patients, young patients with bladder cancer surgery appear to have unique characteristics and a higher overall and cancer specific survival rate.

  8. CYLD, a deubiquitinase specific for lysine63-linked polyubiquitins, accumulates at the postsynaptic density in an activity-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Dosemeci, Ayse, E-mail: dosemeca@mail.nih.gov [Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 (United States); Thein, Soe; Yang, Yijung; Reese, Thomas S. [Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 (United States); Tao-Cheng, Jung-Hwa [EM Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer CYLD is a deubiquitinase specific for lysine63-linked polyubiquitins. Black-Right-Pointing-Pointer Presence of CYLD in PSDs is established by biochemistry and immunoEM. Black-Right-Pointing-Pointer CYLD accumulates on PSDs upon depolarization of neurons. Black-Right-Pointing-Pointer Accumulation of CYLD at PSDs may regulate trafficking/degradation of synaptic proteins. -- Abstract: Polyubiquitin chains on proteins flag them for distinct fates depending on the type of polyubiquitin linkage. While lysine48-linked polyubiquitination directs proteins to proteasomal degradation, lysine63-linked polyubiquitination promotes different protein trafficking and is involved in autophagy. Here we show that postsynaptic density (PSD) fractions from adult rat brain contain deubiquitinase activity that targets both lysine48 and lysine63-linked polyubiquitins. Comparison of PSD fractions with parent subcellular fractions by Western immunoblotting reveals that CYLD, a deubiquitinase specific for lysine63-linked polyubiquitins, is highly enriched in the PSD fraction. Electron microscopic examination of hippocampal neurons in culture under basal conditions shows immunogold label for CYLD at the PSD complex in approximately one in four synapses. Following depolarization by exposure to high K+, the proportion of CYLD-labeled PSDs as well as the labeling intensity of CYLD at the PSD increased by more than eighty percent, indicating that neuronal activity promotes accumulation of CYLD at the PSD. An increase in postsynaptic CYLD following activity would promote removal of lysine63-polyubiquitins from PSD proteins and thus could regulate their trafficking and prevent their autophagic degradation.

  9. The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program.

    Science.gov (United States)

    Nichols, John H; Loeb, Stacy; Metter, E Jeffrey; Ferrucci, Luigi; Carter, H Ballentine

    2012-05-01

    Study Type--Prognostic (cohort). Level of Evidence 2b. What's known on the subject? And what does the study add? Previous studies have attempted to characterize the normal biological variability in PSA among men without prostate cancer. These reports suggest that PSA variability is unrelated to age, but there are conflicting data on its association with the baseline PSA level. There are limited published data regarding the effects of prostate volume on PSA variability. A prior study assessing whether prostate volume changes would confound the use of PSA velocity in clinical practice reported that prostate volume changes were not significantly related to PSA changes. This study did not directly address the effect of baseline prostate volume on serial PSA variability. The objective of the current study was to further examine the relationship between prostate volume and PSA variability. Our hypothesis was that larger baseline prostate volume would be associated with increased PSA variability in men without known prostate cancer and in those with suspected small-volume disease. The results of the study suggest that baseline PSA, not prostate volume, is the primary driver of PSA variability in these populations. • To clarify the relationship between serial prostate-specific antigen (PSA) variability and prostate volume in both cancer-free participants from the Baltimore Longitudinal Study of Aging (BLSA) and patients with low-risk prostate cancer from the Johns Hopkins Active Surveillance Program (AS). • In all, 287 men from the BLSA and 131 patients from the AS were included in the analysis, all with at least two PSA measurements and concurrent prostate volume measurements. • PSA variability was calculated in ng/mL per year, and a linear mixed-effects model was used to determine the relative effects of prostate volume, baseline PSA and age on PSA change over time. • In a model with prostate volume, age and baseline PSA, there was no significant relationship

  10. Induction of apoptosis by Fe(salenCl through caspase-dependent pathway specifically in tumor cells

    Directory of Open Access Journals (Sweden)

    Nitika Pradhan

    2017-10-01

    Full Text Available Iron-based compounds possess the capability of inducing cell death due to their reactivity with oxidant molecules, but their specificity towards cancer cells and the mechanism of action are hitherto less investigated. A Fe(salenCl derivative has been synthesized that remains active in monomer form. The efficacy of this compound as an anti-tumor agent has been investigated in mouse and human leukemia cell lines. Fe(salenCl induces cell death specifically in tumor cells and not in primary cells. Mouse and human T-cell leukemia cell lines, EL4 and Jurkat cells are found to be susceptible to Fe(salenCl and undergo apoptosis, but normal mouse spleen cells and human peripheral blood mononuclear cells (PBMC remain largely unaffected by Fe(salenCl. Fe(salenCl treated tumor cells show significantly higher expression level of cytochrome c that might have triggered the cascade of reactions leading to apoptosis in cancer cells. A significant loss of mitochondrial membrane potential upon Fe(salenCl treatment suggests that Fe(salenCl induces apoptosis by disrupting mitochondrial membrane potential and homeostasis, leading to cytotoxity. We also established that apoptosis in the Fe(salenCl-treated tumor cells is mediated through caspase-dependent pathway. This is the first report demonstrating that Fe(salenCl can specifically target the tumor cells, leaving the primary cells least affected, indicating an excellent potential for this compound to emerge as a next-generation anti-tumor drug.

  11. Induction of apoptosis by Fe(salen)Cl through caspase-dependent pathway specifically in tumor cells.

    Science.gov (United States)

    Pradhan, Nitika; Pratheek, B M; Garai, Antara; Kumar, Ashutosh; Meena, Vikram S; Ghosh, Shyamasree; Singh, Sujay; Kumari, Shikha; Chandrashekar, T K; Goswami, Chandan; Chattopadhyay, Subhasis; Kar, Sanjib; Maiti, Prasanta K

    2014-10-01

    Iron-based compounds possess the capability of inducing cell death due to their reactivity with oxidant molecules, but their specificity towards cancer cells and the mechanism of action are hitherto less investigated. A Fe(salen)Cl derivative has been synthesized that remains active in monomer form. The efficacy of this compound as an anti-tumor agent has been investigated in mouse and human leukemia cell lines. Fe(salen)Cl induces cell death specifically in tumor cells and not in primary cells. Mouse and human T-cell leukemia cell lines, EL4 and Jurkat cells are found to be susceptible to Fe(salen)Cl and undergo apoptosis, but normal mouse spleen cells and human peripheral blood mononuclear cells (PBMC) remain largely unaffected by Fe(salen)Cl. Fe(salen)Cl treated tumor cells show significantly higher expression level of cytochrome c that might have triggered the cascade of reactions leading to apoptosis in cancer cells. A significant loss of mitochondrial membrane potential upon Fe(salen)Cl treatment suggests that Fe(salen)Cl induces apoptosis by disrupting mitochondrial membrane potential and homeostasis, leading to cytotoxity. We also established that apoptosis in the Fe(salen)Cl-treated tumor cells is mediated through caspase-dependent pathway. This is the first report demonstrating that Fe(salen)Cl can specifically target the tumor cells, leaving the primary cells least affected, indicating an excellent potential for this compound to emerge as a next-generation anti-tumor drug. © 2014 International Federation for Cell Biology.

  12. Protective effects of estrogen against vascular calcification via estrogen receptor α-dependent growth arrest-specific gene 6 transactivation

    International Nuclear Information System (INIS)

    Nanao-Hamai, Michiko; Son, Bo-Kyung; Hashizume, Tsuyoshi; Ogawa, Sumito; Akishita, Masahiro

    2016-01-01

    Vascular calcification is one of the major complications of cardiovascular disease and is an independent risk factor for myocardial infarction and cardiac death. Postmenopausal women have a higher prevalence of vascular calcification compared with premenopausal women, suggesting protective effects of estrogen (E2). However, the underlying mechanisms of its beneficial effects remain unclear. In the present study, we examined the inhibitory effects of E2 on vascular smooth muscle cell (VSMC) calcification, and found that growth arrest-specific gene 6 (Gas6), a crucial molecule in vascular calcification, is transactivated by estrogen receptor α (ERα) in response to E2. In human aortic smooth muscle cells, physiological levels of E2 inhibited inorganic phosphate (Pi)-induced calcification in a concentration-dependent manner. This inhibitory effect was significantly abolished by MPP, an ERα-selective antagonist, and ERα siRNA, but not by PHTPP, an ERβ-selective antagonist, and ERβ siRNA, implicating an ERα-dependent action. Apoptosis, an essential process for Pi-induced VSMC calcification, was inhibited by E2 in a concentration-dependent manner and further, MPP abolished this inhibition. Mechanistically, E2 restored the inhibited expression of Gas6 and phospho-Akt in Pi-induced apoptosis through ERα. Furthermore, E2 significantly activated Gas6 transcription, and MPP abrogated this E2-dependent Gas6 transactivation. E2-BSA failed to activate Gas6 transcription and to inhibit Ca deposition in VSMC, suggesting beneficial actions of genomic signaling by E2/nuclear ERα. Taken together, these results indicate that E2 exerts inhibitory effects on VSMC apoptosis and calcification through ERα-mediated Gas6 transactivation. These findings indicate a potential therapeutic strategy for the prevention of vascular calcification, especially in postmenopausal women. - Highlights: • E2 inhibits Pi-induced calcification in vascular smooth muscles cells. • E2 inhibits Pi

  13. Chapter 18: Variable Frequency Drive Evaluation Protocol. The Uniform Methods Project: Methods for Determining Energy Efficiency Savings for Specific Measures

    Energy Technology Data Exchange (ETDEWEB)

    Romberger, Jeff [SBW Consulting, Inc., Bellevue, WA (United States)

    2017-06-21

    An adjustable-speed drive (ASD) includes all devices that vary the speed of a rotating load, including those that vary the motor speed and linkage devices that allow constant motor speed while varying the load speed. The Variable Frequency Drive Evaluation Protocol presented here addresses evaluation issues for variable-frequency drives (VFDs) installed on commercial and industrial motor-driven centrifugal fans and pumps for which torque varies with speed. Constant torque load applications, such as those for positive displacement pumps, are not covered by this protocol.

  14. An Analysis of the Effectiveness of Supplemental Instruction: The Problem of Selection Bias and Limited Dependent Variables

    Science.gov (United States)

    Bowles, Tyler J.; Jones, Jason

    2004-01-01

    Single equation regression models have been used rather extensively to test the effectiveness of Supplemental Instruction (SI). This approach, however, fails to account for the possibility that SI attendance and the outcome of SI attendance are jointly determined endogenous variables. Moreover, the standard approach fails to account for the fact…

  15. High-Rate Pacing Reduces Variability of Repolarization and Prevents Repolarization-Dependent Arrhythmias in Dogs With Chronic AV Block

    DEFF Research Database (Denmark)

    Oosterhoff, Peter; Thomsen, Morten Bækgaard; Maas, Joep N

    2010-01-01

    -term variability of repolarization (STV) as a feedback parameter of arrhythmic risk. Methods and Results: The minimal signal sampling frequency required for measuring STV was determined through computer simulation. Arrhythmogenic response to dofetilide (25 µg/kg/5minutes) was tested at two different paced heart...

  16. Presentation of valid correlations in some morphological variables and basic and specific motor skills in young people aged 13-14 years engaged in basketball

    Directory of Open Access Journals (Sweden)

    Florian Miftari

    2018-05-01

    Full Text Available Study-research deals with younger students of both sexes aged 13-14, who, besides attending classes of physical education and sports, also practice in basketball schools in the city of Pristina. The experiment contains a total of 7 morphological variables, while four tests of basic motion skills and seven variables are from specific motion skills. In this study, the verification and analysis of the correlation of morphological characteristics and basic and situational motor skills in both groups of both sexes (boys and girls were treated. Based on the results obtained between several variables, valid correlations with high coefficients are presented, whereas among the variables are presented correlations with optimal values. The experimentation in question includes the number of 80 entities of both sexes; the group of 40 boys and the other group consisting of 40 girls who have undergone the tests for this study-experiment.

  17. SU-C-BRA-07: Variability of Patient-Specific Motion Models Derived Using Different Deformable Image Registration Algorithms for Lung Cancer Stereotactic Body Radiotherapy (SBRT) Patients

    Energy Technology Data Exchange (ETDEWEB)

    Dhou, S; Williams, C [Brigham and Women’s Hospital / Harvard Medical School, Boston, MA (United States); Ionascu, D [William Beaumont Hospital, Royal Oak, MI (United States); Lewis, J [University of California at Los Angeles, Los Angeles, CA (United States)

    2016-06-15

    Purpose: To study the variability of patient-specific motion models derived from 4-dimensional CT (4DCT) images using different deformable image registration (DIR) algorithms for lung cancer stereotactic body radiotherapy (SBRT) patients. Methods: Motion models are derived by 1) applying DIR between each 4DCT image and a reference image, resulting in a set of displacement vector fields (DVFs), and 2) performing principal component analysis (PCA) on the DVFs, resulting in a motion model (a set of eigenvectors capturing the variations in the DVFs). Three DIR algorithms were used: 1) Demons, 2) Horn-Schunck, and 3) iterative optical flow. The motion models derived were compared using patient 4DCT scans. Results: Motion models were derived and the variations were evaluated according to three criteria: 1) the average root mean square (RMS) difference which measures the absolute difference between the components of the eigenvectors, 2) the dot product between the eigenvectors which measures the angular difference between the eigenvectors in space, and 3) the Euclidean Model Norm (EMN), which is calculated by summing the dot products of an eigenvector with the first three eigenvectors from the reference motion model in quadrature. EMN measures how well an eigenvector can be reconstructed using another motion model derived using a different DIR algorithm. Results showed that comparing to a reference motion model (derived using the Demons algorithm), the eigenvectors of the motion model derived using the iterative optical flow algorithm has smaller RMS, larger dot product, and larger EMN values than those of the motion model derived using Horn-Schunck algorithm. Conclusion: The study showed that motion models vary depending on which DIR algorithms were used to derive them. The choice of a DIR algorithm may affect the accuracy of the resulting model, and it is important to assess the suitability of the algorithm chosen for a particular application. This project was supported

  18. SU-C-BRA-07: Variability of Patient-Specific Motion Models Derived Using Different Deformable Image Registration Algorithms for Lung Cancer Stereotactic Body Radiotherapy (SBRT) Patients

    International Nuclear Information System (INIS)

    Dhou, S; Williams, C; Ionascu, D; Lewis, J

    2016-01-01

    Purpose: To study the variability of patient-specific motion models derived from 4-dimensional CT (4DCT) images using different deformable image registration (DIR) algorithms for lung cancer stereotactic body radiotherapy (SBRT) patients. Methods: Motion models are derived by 1) applying DIR between each 4DCT image and a reference image, resulting in a set of displacement vector fields (DVFs), and 2) performing principal component analysis (PCA) on the DVFs, resulting in a motion model (a set of eigenvectors capturing the variations in the DVFs). Three DIR algorithms were used: 1) Demons, 2) Horn-Schunck, and 3) iterative optical flow. The motion models derived were compared using patient 4DCT scans. Results: Motion models were derived and the variations were evaluated according to three criteria: 1) the average root mean square (RMS) difference which measures the absolute difference between the components of the eigenvectors, 2) the dot product between the eigenvectors which measures the angular difference between the eigenvectors in space, and 3) the Euclidean Model Norm (EMN), which is calculated by summing the dot products of an eigenvector with the first three eigenvectors from the reference motion model in quadrature. EMN measures how well an eigenvector can be reconstructed using another motion model derived using a different DIR algorithm. Results showed that comparing to a reference motion model (derived using the Demons algorithm), the eigenvectors of the motion model derived using the iterative optical flow algorithm has smaller RMS, larger dot product, and larger EMN values than those of the motion model derived using Horn-Schunck algorithm. Conclusion: The study showed that motion models vary depending on which DIR algorithms were used to derive them. The choice of a DIR algorithm may affect the accuracy of the resulting model, and it is important to assess the suitability of the algorithm chosen for a particular application. This project was supported

  19. Variable Extent of Lineage-Specificity and Developmental Stage-Specificity of Cohesin and CCCTC-Binding Factor Binding Within the Immunoglobulin and T Cell Receptor Loci

    Directory of Open Access Journals (Sweden)

    Salvatore Loguercio

    2018-03-01

    Full Text Available CCCTC-binding factor (CTCF is largely responsible for the 3D architecture of the genome, in concert with the action of cohesin, through the creation of long-range chromatin loops. Cohesin is hypothesized to be the main driver of these long-range chromatin interactions by the process of loop extrusion. Here, we performed ChIP-seq for CTCF and cohesin in two stages each of T and B cell differentiation and examined the binding pattern in all six antigen receptor (AgR loci in these lymphocyte progenitors and in mature T and B cells, ES cells, and fibroblasts. The four large AgR loci have many bound CTCF sites, most of which are only occupied in lymphocytes, while only the CTCF sites at the end of each locus near the enhancers or J genes tend to be bound in non-lymphoid cells also. However, despite the generalized lymphocyte restriction of CTCF binding in AgR loci, the Igκ locus is the only locus that also shows significant lineage-specificity (T vs. B cells and developmental stage-specificity (pre-B vs. pro-B in CTCF binding. We show that cohesin binding shows greater lineage- and stage-specificity than CTCF at most AgR loci, providing more specificity to the loops. We also show that the culture of pro-B cells in IL7, a common practice to expand the number of cells before ChIP-seq, results in a CTCF-binding pattern resembling pre-B cells, as well as other epigenetic and transcriptional characteristics of pre-B cells. Analysis of the orientation of the CTCF sites show that all sites within the large V portions of the Igh and TCRβ loci have the same orientation. This suggests either a lack of requirement for convergent CTCF sites creating loops, or indicates an absence of any loops between CTCF sites within the V region portion of those loci but only loops to the convergent sites at the D-J-enhancer end of each locus. The V region portions of the Igκ and TCRα/δ loci, by contrast, have CTCF sites in both orientations, providing many options for

  20. Cytoskeletal protein translation and expression in the rat brain are stressor-dependent and region-specific.

    Directory of Open Access Journals (Sweden)

    Petra Sántha

    Full Text Available Stress is an integral component of life that can sometimes cause a critical overload, depending on the qualitative and quantitative natures of the stressors. The involvement of actin, the predominant component of dendritic integrity, is a plausible candidate factor in stress-induced neuronal cytoskeletal changes. The major aim of this study was to compare the effects of three different stress conditions on the transcription and translation of actin-related cytoskeletal genes in the rat brain. Male Wistar rats were exposed to one or other of the frequently used models of physical stress, i.e. electric foot shock stress (EFSS, forced swimming stress (FSS, or psychosocial stress (PSS for periods of 3, 7, 14, or 21 days. The relative mRNA and protein expressions of β-actin, cofilin and mitogen-activated protein kinase 1 (MAPK-1 were determined by qRT- PCR and western blotting from hippocampus and frontal cortex samples. Stressor-specific alterations in both β-actin and cofilin expression levels were seen after stress. These alterations were most pronounced in response to EFSS, and exhibited a U-shaped time course. FSS led to a significant β-actin mRNA expression elevation in the hippocampus and the frontal cortex after 3 and 7 days, respectively, without any subsequent change. PSS did not cause any change in β-actin or cofilin mRNA or protein expression in the examined brain regions. EFSS, FSS and PSS had no effect on the expression of MAPK-1 mRNA at any tested time point. These findings indicate a very delicate, stress type-dependent regulation of neuronal cytoskeletal components in the rat hippocampus and frontal cortex.

  1. Dual effect of fetal bovine serum on early development depends on stage-specific reactive oxygen species demands in pigs.

    Directory of Open Access Journals (Sweden)

    Seong-Eun Mun

    Full Text Available Despite the application of numerous supplements to improve in vitro culture (IVC conditions of mammalian cells, studies regarding the effect of fetal bovine serum (FBS on mammalian early embryogenesis, particularly in relation to redox homeostasis, are lacking. Herein, we demonstrated that early development of in vitro-produced (IVP porcine embryos highly depends on the combination of FBS supplementation timing and embryonic reactive oxygen species (ROS requirements. Interestingly, FBS significantly reduced intracellular ROS levels in parthenogenetically activated (PA embryos regardless of the developmental stage. However, the beneficial effect of FBS on early embryogenesis was found only during the late phase (IVC 4-6 days treatment group. In particular, developmental competence parameters, such as blastocyst formation rate, cellular survival, total cell number and trophectoderm proportion, were markedly increased by FBS supplementation during the late IVC phase. In addition, treatment with FBS elevated antioxidant transcript levels during the late IVC phase. In contrast, supplementation with FBS during the entire period (1-6 days or during the early IVC phase (1-2 days greatly impaired the developmental parameters. Consistent with the results from PA embryos, the developmental competence of in vitro fertilization (IVF or somatic cell nuclear transfer (SCNT embryos were markedly improved by treatment with FBS during the late IVC phase. Moreover, the embryonic stage-specific effects of FBS were reversed by the addition of an oxidant and were mimicked by treatment with an antioxidant. These findings may increase our understanding of redox-dependent early embryogenesis and contribute to the large-scale production of high-quality IVP embryos.

  2. Upper and lower solutions for BVPs on the half-line with variable coefficient and derivative depending nonlinearity

    Directory of Open Access Journals (Sweden)

    S. Djebali

    2011-02-01

    Full Text Available This paper is concerned with a second-order nonlinear boundary value problem with a derivative depending nonlinearity and posed on the positive half-line. The derivative operator is time dependent. Upon a priori estimates and under a Nagumo growth condition, the Schauder's fixed point theorem combined with the method of upper and lower solutions on unbounded domains are used to prove existence of solutions. A uniqueness theorem is also obtained and some examples of application illustrate the obtained results.

  3. A similarity solution of time dependent MHD liquid film flow over stretching sheet with variable physical properties

    Directory of Open Access Journals (Sweden)

    M. Idrees

    2018-03-01

    Full Text Available An analysis is performed for the fluid dynamics incorporating the variation of viscosity and thermal conductivity on an unsteady two-dimensional free surface flow of a viscous incompressible conducting fluid taking into account the effect of a magnetic field. Surface tension quadratically vary with temperature while fluid viscosity and thermal conductivity are assumed to vary as a linear function of temperature. The boundary layer partial differential equations in cartesian coordinates are transformed into a system of nonlinear ordinary differential equations (ODEs by similarity transformation. The developed nonlinear equations are solved analytically by Homotopy Analysis Method (HAM while numerically by using the shooting method. The Effects of natural parameters such as the variable viscosity parameter A, variable thermal conductivity parameter N, Hartmann number Ma, film Thickness, unsteadiness parameter S, Thermocapillary number M and Prandtl number Pr on the velocity and temperature profiles are investigated. The results for the surface skin friction coefficient f″(0, Nusselt number (heat flux -θ′(0 and free surface temperature θ(1 are presented graphically and in tabular form. Keywords: Variable viscosity and thermal conductivity, Thermocapillary number, Magnetic field, Thin film, Unsteady stretching surface

  4. The IL--6 dependent effect of oral warfarin in heart valve replacement patients by measuring interacting clinical and demographic variables

    International Nuclear Information System (INIS)

    Shafiq, H.; Rashid, A.; Majeed, A.; Razah, S.; Asghar, I.

    2016-01-01

    Objective: To examine an inflammatory effect of warfarin and comparing with IL-6 levels along with different demographic and clinical variables. Study Design: Quasi experimental study. Place and Duration of Study: Center of Research in Experimental and Applied Medicine (CREAM), Army Medical College/National University of Sciences and Technology, Islamabad from Oct 2013 to Oct 2015. Material and Methods: The study design was Quasi Experimental study. Samples were collected by Non probability convenience sampling. Total 76 patients were included according to warfarin dose response in warfarin therapy patients, i.e. 32(42 percent) were taking 10mg/day of warfarin dose. Patient's demographic and clinical variables were noted i.e. age, gender, BMI, duration of therapy, INR history, hepatic, gastrointestinal and diabetic complications. Human IL-6 ELISA assay was performed. Results: The statistically significant difference was found between age groups (in years) and different levels of warfarin dose (p=0.046) along with IL-6 production. There is a negative correlation between warfarin dose and age group i.e. as age increases, the dose of warfarin decreases. Among the inter and intra-patient variability age and serum IL-6 levels were found to be statistically significant with warfarin dose response. BMI and warfarin dose were found to be weak positively correlated. Conclusion: A marked immunomodulatory response of warfarin was noted by measuring IL-6 levels. IL-6 levels retained a significant association with warfarin dose. (author)

  5. Age- and stage-dependent variations of muscle-specific gene expression in brown trout Salmo trutta L.

    Science.gov (United States)

    Churova, Maria V; Meshcheryakova, Olga V; Ruchev, Mikhail; Nemova, Nina N

    2017-09-01

    This study was conducted to characterize the features of muscle-specific genes expression during development of brown trout Salmo trutta inhabiting the river Krivoy ruchey (Kola Peninsula, Russia). Gene expression levels of myogenic regulatory factors (MRFs - MyoD1 paralogs (MyoD1a, MyoD1b, MyoD1c), Myf5, myogenin), myostatin paralogs (MSTN-1a, MSTN-1b, MSTN-2a), fast skeletal myosin heavy chain (MyHC) were measured in the white muscles of brown trout parr of ages 0+ (under-yearling), 1+ (yearling) and 2+ (two year old) and smolts of age 2+. Multidirectional changes in MyoD1 and MSTN paralogs expression along with myogenin, Myf 5 and MyHC expression levels in white muscles in parr of trout with age were revealed. The expression of MyoD1c, myogenin, MSTN-2a was the highest in 0+ parr and then decreased. MyoD1a/b expression levels didn't differ between age groups. The simultaneous elevation of MyHC, Myf5, MSTN-1a, and MSTN-1b was found in trout yearlings. In smolts, expression levels of MSTN paralogs, MyHC, Myf5, MyoD1a was lower than in parr. But in contrast, the MyoD1c and myogenin mRNA levels was higher in smolts. The study revealed that there are definite patterns in simultaneous muscle-specific genes expression in age groups of parr and smolts. As MyoD and MSTN paralogs expression changed differently in dependence on age and stage, it was suggested that paralogs of the same gene complementarily control myogenesis during development. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Age-dependent trigeminal and female-specific lumbosacral increase in herpes zoster distribution in the elderly.

    Science.gov (United States)

    Shiraki, Kimiyasu; Toyama, Nozomu; Shiraki, Atsuko; Yajima, Misako

    2018-05-01

    Varicella-zoster virus causes herpes zoster (HZ) along specific dermatomes, but the effects of age and sex on HZ distribution are unclear. We investigated the age- and sex-dependent distribution characteristics of HZ. Patients with HZ were monitored by members of the Miyazaki Dermatologist Society. Questionnaires containing information on age, sex, and dermatome distribution and lesion specimens from 2730 patients were collected, and 2508 PCR-diagnosed cases were analyzed. The ratio of lesions in the thoracic area to lesions in the whole body decreased with age, whereas those of other areas increased. HZ incidence increased with age to about four times that of the basic incidence in the dermatome areas at age 0-29 years; the incidence in the trigeminal area in both sexes increased 11-fold, and the incidence in the thoracic and lumbosacral areas increased in females more than in males. Furthermore, the fact that the highest incidence was found along the first branch of the trigeminal nerve suggests an association with long-term ultraviolet ray exposure. Segmental dermatomes comprising thoracic 10-lumbar 1/sacral 2-4 and thoracic 5-6 were significantly more frequently affected in female patients at age 50-59 years and are consistent with areas of obstetric anesthesia for childbirth and of breastfeeding, respectively. HZ incidence increased with age; moreover, exposure to ultraviolet rays, childbirth, and breastfeeding might increase the incidence at specific dermatomes in older individuals. This study provides important information on the etiology of HZ. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  7. Protection against Syphilis Correlates with Specificity of Antibodies to the Variable Regions of Treponema pallidum Repeat Protein K

    OpenAIRE

    Morgan, Cecilia A.; Lukehart, Sheila A.; Van Voorhis, Wesley C.

    2003-01-01

    Syphilis has been recognized as a disease since the late 1400s, yet there is no practical vaccine available. One impediment to the development of a vaccine is the lack of understanding of multiple reinfections in humans despite the development of robust immune responses during the first episode. It has been shown that the Treponema pallidum repeat protein K (TprK) differs in seven discrete variable (V) regions in isolates and that the antibody response during infection is directed to these V ...

  8. The Association of Selected Conative Variables to Field-Dependence with Inferences for Reasoning Characteristics in Marketing Education.

    Science.gov (United States)

    Fritz, Robert L.

    A study examined the association between field-dependence and its related information processing characteristics, and educational cognitive style as a model of conative influence. Data were collected from 145 secondary marketing education students in nothern Georgia during spring 1991. Descriptive statistics, Pearson product moment correlations,…

  9. Island-specific preferences of tourists for environmental features: implications of climate change for tourism dependent states

    Energy Technology Data Exchange (ETDEWEB)

    Uyarra, M.C.; Cote, I.M. [East Anglia Univ., Norwich (United Kingdom). Centre for Ecology, Evolution and Conservation; Gill, J.A. [East Anglia Univ., Norwich (United Kingdom). School of Environmental Sciences; Tyndall Centre for Climate Change Research, Norwich (United Kingdom); Tinch, R.T. [East Anglia Univ., Norwich (United Kingdom). School of Environmental Sciences; Macaulay Land Use Research Inst., Aberdeen (United Kingdom); Viner, D. [East Anglia Univ., Norwich (United Kingdom). Climate Research Unit; Watkinson, A.R. [East Anglia Univ., Norwich (United Kingdom). Centre for Ecology, Evolution and Conservation; East Anglia Univ., Norwich (United Kingdom). School of Environmental Sciences

    2005-03-15

    Climate change may affect important environmental components of holiday destinations, which might have repercussions for tourism-dependent economies. This study documents the importance of environmental attributes in determining the choice and holiday enjoyment of tourists visiting Bonaire and Barbados, two Caribbean islands with markedly different tourism markets and infrastructure. Three hundred and sixteen and 338 participants from Bonaire and Barbados, respectively, completed standardized questionnaires. Warm temperatures, clear waters and low health risks were the most important environmental features determining holiday destination choice. However, tourists in Bonaire thereafter prioritized marine wildlife attributes (i.e. coral and fish diversity and abundance) over other environmental features, whereas tourists in Barbados exhibited stronger preferences for terrestrial features, particularly beach characteristics. The willingness of tourists to revisit these islands was strongly linked to the state of the preferred environmental attributes. More than 80% of tourists in Bonaire and Barbados would be unwilling to return for the same holiday price in the event, respectively, of coral bleaching as a result of elevated sea surface temperatures and reduced beach area as a result of sea level rise. Climate change might have a significant impact on Caribbean tourism economy through alteration of environmental features important to destination selection. Island-specific management strategies, such as focusing resources on the protection of key marine or terrestrial features, may provide a means of reducing the environmental and economic impacts of climate change. (author)

  10. Cloning of a cDNA encoding the human cation-dependent mannose 6-phosphate-specific receptor

    International Nuclear Information System (INIS)

    Pohlmann, R.; Nagel, G.; Schmidt, B.

    1987-01-01

    Complementary DNA clones for the human cation-dependent mannose 6-phosphate-specific receptor have been isolated from a human placenta library in λgt11. The nucleotide sequence of the 2463-base-pair cDNA insert includes a 145-base-pair 5' untranslated region, an open reading frame of 831 base pairs corresponding to 277 amino acids, and a 1487-base-pair 3' untranslated region. The deduced amino acid sequence is colinear with that determined by amino acid sequencing of the N-terminus peptide (41 residues) and nine tryptic peptides (93 additional residues). The receptor is synthesized as a precursor with a signal peptide of 20 amino acids. The hydrophobicity profile of the receptor indicates a single membrane-spanning domain, which separates an N-terminal region containing five potential N-glycosylation sites from a C-terminal region lacking N-glycosylation sites. Thus the N-terminal (M/sub r/ = 18,299) and C-terminal (M/sub r/ ≤ 7648) segments of the mature receptor are assumed to be exposed to the extracytosolic and cytosolic sides of the membrane, respectively. Analysis of a panel of somatic cell (mouse-human) hybrids shows that the gene for the receptor is located on human chromosome 12

  11. Enzyme Sorption onto Soil and Biocarbon Amendments Alters Catalytic Capacity and Depends on the Specific Protein and pH

    Science.gov (United States)

    Foster, E.; Fogle, E. J.; Cotrufo, M. F.

    2017-12-01

    Enzymes catalyze biogeochemical reactions in soils and play a key role in nutrient cycling in agricultural systems. Often, to increase soil nutrients, agricultural managers add organic amendments and have recently experimented with charcoal-like biocarbon products. These amendments can enhance soil water and nutrient holding capacity through increasing porosity. However, the large surface area of the biocarbon has the potential to sorb nutrients and other organic molecules. Does the biocarbon decrease nutrient cycling through sorption of enzymes? In a laboratory setting, we compared the interaction of two purified enzymes β-glucosidase and acid phosphatase with a sandy clay loam and two biocarbons. We quantified the sorbed enzymes at three different pHs using a Bradford protein assay and then measured the activity of the sorbed enzyme via high-throughput fluorometric analysis. Both sorption and activity depended upon the solid phase, pH, and specific enzyme. Overall the high surface area biocarbon impacted the catalytic capacity of the enzymes more than the loam soil, which may have implications for soil nutrient management with these organic amendments.

  12. Casein Hydrolysates by Lactobacillus brevis and Lactococcus lactis Proteases: Peptide Profile Discriminates Strain-Dependent Enzyme Specificity.

    Science.gov (United States)

    Bounouala, Fatima Zohra; Roudj, Salima; Karam, Nour-Eddine; Recio, Isidra; Miralles, Beatriz

    2017-10-25

    Casein from ovine and bovine milk were hydrolyzed with two extracellular protease preparations from Lactobacillus brevis and Lactococcus lactis. The hydrolysates were analyzed by HPLC-MS/MS for peptide identification. A strain-dependent peptide profile could be observed, regardless of the casein origin, and the specificity of these two proteases could be computationally ascribed. The cleavage pattern yielding phenylalanine, leucine, or tyrosine at C-terminal appeared both at L. lactis and Lb. brevis hydrolysates. However, the cleavage C-terminal to lysine was favored with Lb. brevis protease. The hydrolysates showed ACE-inhibitory activity with IC 50 in the 16-70 μg/mL range. Ovine casein hydrolysates yielded greater ACE-inhibitory activity. Previously described antihypertensive and opioid peptides were found in these ovine and bovine casein hydrolysates and prediction of the antihypertensive activity of the sequences based on quantitative structure and activity relationship (QSAR) was performed. This approach might represent a useful classification tool regarding health-related properties prior to further purification.

  13. Cell-Type-Specific Circuit Connectivity of Hippocampal CA1 Revealed through Cre-Dependent Rabies Tracing

    Directory of Open Access Journals (Sweden)

    Yanjun Sun

    2014-04-01

    Full Text Available We developed and applied a Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to specific CA1 neuron types in the mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, the entorhinal cortex (EC, the medial septum (MS, and, unexpectedly, the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons, whereas inhibitory neurons receive a great majority of inputs from GABAergic MS neurons. Both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons received much stronger input than SOM+ neurons from CA3, the EC, and the MS. Thus, rabies tracing identifies hippocampal circuit connections and maps how the different input sources to CA1 are distributed with different strengths on each of its constituent cell types.

  14. The dopamine transporter gene may not contribute to susceptibility and the specific personality traits of amphetamine dependence.

    Science.gov (United States)

    Tzeng, Nian-Sheng; Lu, Ru-Band; Yeh, Hui-Wen; Yeh, Yi-Wei; Huang, Chang-Chih; Yen, Che-Hung; Kuo, Shin-Chang; Chen, Chun-Yen; Chang, Hsin-An; Ho, Pei-Shen; Cheng, Serena; Shih, Mei-Chen; Huang, San-Yuan

    2015-04-01

    A substantial amount of evidence suggests that dysfunction of the dopamine transporter may be involved in the pathophysiology of amphetamine dependence (AD). The aim of this study was to examine whether the dopamine transporter gene (DAT1, SLC6A3) is associated with development of AD and whether this gene influences personality traits in patients with AD. Eighteen polymorphisms of the DAT1 gene were analyzed in a case-control study that included 909 Han Chinese men (568 patients with AD and 341 control subjects). The patients fulfilled the DSM-IV-TR criteria for AD. The Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits and to examine the association between these traits and DAT1 gene variants. A weak association was found between the rs27072 polymorphism and development of AD, but these borderline associations were unconfirmed by logistic regression and haplotype analysis. Although harm avoidance and novelty seeking scores were significantly higher in patients than in controls, DAT1 polymorphisms did not influence these scores. This study suggests that high harm avoidance and novelty seeking personality traits may be a risk factor for the development of AD. However, the DAT1 gene may not contribute to AD susceptibility and specific personality traits observed in AD among Han Chinese men. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Site-Specific Hydrogen Isotope Composition of Propane: Mass spectrometric methods, equilibrium temperature dependence, and kinetics of exchange

    Science.gov (United States)

    Xie, H.; Ponton, C.; Kitchen, N.; Lloyd, M. K.; Lawson, M.; Formolo, M. J.; Eiler, J. M.

    2016-12-01

    Intramolecular isotope ordering can constrain temperatures of synthesis, mechanisms of formation, and/or source substrates of organic compounds. Here we explore site-specific hydrogen isotope variations of propane. Statistical thermodynamic models predict that at equilibrium methylene hydrogen (-CH2-) in propane will be 10's of per mil higher in D/H ratio than methyl hydrogen (-CH3) at geologically relevant temperatures, and that this difference is highly temperature dependent ( 0.5-1 ‰/°C). Chemical-kinetic controls on site-specific D/H in propane could constrain the mechanisms, conditions and extents of propane synthesis or destruction. We have developed a method for measuring the difference in D/H ratio between methylene and methyl hydrogen in propane by gas source mass spectrometry. The data were measured using the Thermo Fisher Double Focusing Sector high resolution mass spectrometer (DFS), and involve comparison of the D/H ratios of molecular ion (C3H8+) and the ethyl fragmental ion (C2H5+). We demonstrate the accuracy and precision of this method through analysis of D-labeled and independently analyzed propanes. In the exchange experiments, propane was heated (100-200 oC) either alone or in the presence of D-enriched water (δD=1,1419 ‰ SMOW), with or without one of several potentially catalytic substrates for hours to weeks. Propane was found to exchange hydrogen with water vigorously at 200 °C in the presence of metal catalysts. In the presence of Ni catalyst, methylene hydrogen exchanges 2.5 times faster than methyl hydrogen. Hydrogen exchange in the presence of Pd catalyst is more effective and can equilibrate hydrogen isotope distribution on propane on the order of 7 days. Isotopic exchange in the presence of natural materials have also been tested, but is only measurable in the methylene group at 200 °C. High catalytic activity of Pd permits attainment of a bracketed, time-invariant equilibrium state that we use to calibrate the site-specific

  16. Cell-type-specific and differentiation-status-dependent variations in cytotoxicity of tributyltin in cultured rat cerebral neurons and astrocytes.

    Science.gov (United States)

    Oyanagi, Koshi; Tashiro, Tomoko; Negishi, Takayuki

    2015-08-01

    Tributyltin (TBT) is an organotin used as an anti-fouling agent for fishing nets and ships and it is a widespread environmental contaminant at present. There is an increasing concern about imperceptible but serious adverse effect(s) of exposure to chemicals existing in the environment on various organs and their physiological functions, e.g. brain and mental function. Here, so as to contribute to improvement of and/or advances in in vitro cell-based assay systems for evaluating brain-targeted adverse effect of chemicals, we tried to evaluate cell-type-specific and differentiation-status-dependent variations in the cytotoxicity of TBT towards neurons and astrocytes using the four culture systems differing in the relative abundance of these two types of cells; primary neuron culture (> 95% neurons), primary neuron-astrocyte (2 : 1) mix culture, primary astrocyte culture (> 95% astrocytes), and passaged astrocyte culture (100% proliferative astrocytes). Cell viability was measured at 48 hr after exposure to TBT in serum-free medium. IC50's of TBT were 198 nM in primary neuron culture, 288 nM in primary neuron-astrocyte mix culture, 2001 nM in primary astrocyte culture, and 1989 nM in passaged astrocyte culture. Furthermore, in primary neuron-astrocyte mix culture, vulnerability of neurons cultured along with astrocytes to TBT toxicity was lower than that of neurons cultured purely in primary neuron culture. On the other hand, astrocytes in primary neuron-astrocyte mix culture were considered to be more vulnerable to TBT than those in primary or passaged astrocyte culture. The present study demonstrated variable cytotoxicity of TBT in neural cells depending on the culture condition.

  17. Variability Bugs:

    DEFF Research Database (Denmark)

    Melo, Jean

    . Although many researchers suggest that preprocessor-based variability amplifies maintenance problems, there is little to no hard evidence on how actually variability affects programs and programmers. Specifically, how does variability affect programmers during maintenance tasks (bug finding in particular......)? How much harder is it to debug a program as variability increases? How do developers debug programs with variability? In what ways does variability affect bugs? In this Ph.D. thesis, I set off to address such issues through different perspectives using empirical research (based on controlled...... experiments) in order to understand quantitatively and qualitatively the impact of variability on programmers at bug finding and on buggy programs. From the program (and bug) perspective, the results show that variability is ubiquitous. There appears to be no specific nature of variability bugs that could...

  18. Variability of photovoltaic panels efficiency depending on the value of the angle of their inclination relative to the horizon

    Directory of Open Access Journals (Sweden)

    Majdak Marek

    2017-01-01

    Full Text Available The objective of this paper was to determine the relationship between the efficiency of photovoltaic panels and the value of the angle of their inclination relative to the horizon. For the purpose of experimental research have been done tests on the photovoltaic modules made of monocrystalline, polycrystalline and amorphous silicon. The experiment consisted of measurement of the voltage and current generated by photovoltaic panels at a known value of solar radiation and a specified resistance value determined by using resistor with variable value of resistance and known value of the angle of their inclination relative to the horizon.

  19. Identification of variables for site calibration and power curve assessment in complex terrain. Task 8, a literature survey on theory and practice of parameter identification, specification and estimation (ISE) techniques

    Energy Technology Data Exchange (ETDEWEB)

    Verhoef, J.P.; Leendertse, G.P. [ECN Wind, Petten (Netherlands)

    2001-04-01

    This document presents the literature survey results on Identification, Specification and Estimation (ISE) techniques for variables within the SiteParIden project. Besides an overview of the different general techniques also an overview is given on EU funded wind energy projects where some of these techniques have been applied more specifically. The main problem in applications like power performance assessment and site calibration is to establish an appropriate model for predicting the considered dependent variable with the aid of measured independent (explanatory) variables. In these applications detailed knowledge on what the relevant variables are and how their precise appearance in the model would be is typically missing. Therefore, the identification (of variables) and the specification (of the model relation) are important steps in the model building phase. For the determination of the parameters in the model a reliable variable estimation technique is required. In EU funded wind energy projects the linear regression technique is the most commonly applied tool for the estimation step. The linear regression technique may fail in finding reliable parameter estimates when the model variables are strongly correlated, either due to the experimental set-up or because of their particular appearance in the model. This situation of multicollinearity sometimes results in unrealistic parameter values, e.g. with the wrong algebraic sign. It is concluded that different approaches, like multi-binning can provide a better way of identifying the relevant variables. However further research in these applications is needed and it is recommended that alternative methods (neural networks, singular value decomposition etc.) should also be tested on their usefulness in a succeeding project. Increased interest in complex terrains, as feasible locations for wind farms, has also emphasised the need for adequate models. A common standard procedure to prescribe the statistical

  20. A similarity solution of time dependent MHD liquid film flow over stretching sheet with variable physical properties

    Science.gov (United States)

    Idrees, M.; Rehman, Sajid; Shah, Rehan Ali; Ullah, M.; Abbas, Tariq

    2018-03-01

    An analysis is performed for the fluid dynamics incorporating the variation of viscosity and thermal conductivity on an unsteady two-dimensional free surface flow of a viscous incompressible conducting fluid taking into account the effect of a magnetic field. Surface tension quadratically vary with temperature while fluid viscosity and thermal conductivity are assumed to vary as a linear function of temperature. The boundary layer partial differential equations in cartesian coordinates are transformed into a system of nonlinear ordinary differential equations (ODEs) by similarity transformation. The developed nonlinear equations are solved analytically by Homotopy Analysis Method (HAM) while numerically by using the shooting method. The Effects of natural parameters such as the variable viscosity parameter A, variable thermal conductivity parameter N, Hartmann number Ma, film Thickness, unsteadiness parameter S, Thermocapillary number M and Prandtl number Pr on the velocity and temperature profiles are investigated. The results for the surface skin friction coefficient f″ (0) , Nusselt number (heat flux) -θ‧ (0) and free surface temperature θ (1) are presented graphically and in tabular form.

  1. General and Specific Contributions of RAN to Reading and Arithmetic Fluency in First Graders: A Longitudinal Latent Variable Approach.

    Science.gov (United States)

    Hornung, Caroline; Martin, Romain; Fayol, Michel

    2017-01-01

    In the present study, we opted for a longitudinal design and examined rapid automatized naming (RAN) performance from two perspectives. In a first step, we examined the structure of RAN performance from a general cognitive perspective. We investigated whether rapid naming measures (e.g., digit RAN and color RAN) reflect a mainly domain-general factor or domain-specific factors. In a second step, we examined how the best fitting RAN model was related to reading and arithmetic outcomes, assessed several months later. Finally in a third step we took a clinical perspective and investigated specific contributions of RAN measures to reading and arithmetic outcomes. While RAN has emerged as a promising predictor of reading, the relationship between RAN and arithmetic has been less examined in the past. Hundred and twenty-two first graders completed seven RAN tasks, each comprising visually familiar stimuli such as digits, vowels, consonants, dice, finger-numeral configurations, objects, and colors. Four months later the same children completed a range of reading and arithmetic tasks. From a general descriptive perspective, structural equation modeling supports a one-dimensional RAN factor in 6- to -7-year-old children. However, from a clinical perspective, our findings emphasize the specific contributions of RANs. Interestingly, alphanumeric RANs (i.e., vowel RAN) were most promising when predicting reading skills and number-specific RANs (i.e., finger-numeral configuration RAN) were most promising when predicting arithmetic fluency. The implications for clinical and educational practices will be discussed.

  2. Effects of canopy structural variables on retrieval of leaf dry matter content and specific leaf area from remotely sensed data

    NARCIS (Netherlands)

    Ali, A.M.; Darvishzadeh, R.; Skidmore, A.K.; van Duren, I.C.

    2016-01-01

    Leaf dry matter content (LDMC) and specific leaf area (SLA) are two important traits in measuring biodiversity. To use remote sensing for the estimation of these traits, it is essential to understand the underlying factors that influence their relationships with canopy reflectance. The effect of

  3. Assessing the impact of extreme air temperature on fruit trees by modeling weather dependent phenology with variety-specific thermal requirements

    Science.gov (United States)

    Alfieri, Silvia Maria; De Lorenzi, Francesca; Missere, Daniele; Buscaroli, Claudio; Menenti, Massimo

    2013-04-01

    Extremely high and extremely low temperature may have a terminal impact on the productivity of fruit tree if occurring at critical phases of development. Notorious examples are frost during flowering or extremely high temperature during fruit setting. The dates of occurrence of such critical phenological stages depend on the weather history from the start of the yearly development cycle in late autumn, thus the impact of climate extremes can only be evaluated correctly if the phenological development is modeled taking into account the weather history of the specific year being evaluated. Climate change impact may lead to a shift in timing of phenological stages and change in the duration of vegetative and reproductive phases. A changing climate can also exhibit a greater climatic variability producing quite large changes in the frequency of extreme climatic events. We propose a two-stage approach to evaluate the impact of predicted future climate on the productivity of fruit trees. The phenological development is modeled using phase - specific thermal times and variety specific thermal requirements for several cultivars of pear, apricot and peach. These requirements were estimated using phenological observations over several years in Emilia Romagna region and scientific literature. We calculated the dates of start and end of rest completion, bud swell, flowering, fruit setting and ripening stages , from late autumn through late summer. Then phase-specific minimum and maximum cardinal temperature were evaluated for present and future climate to estimate how frequently they occur during any critically sensitive phenological phase. This analysis has been done for past climate (1961 - 1990) and fifty realizations of a year representative of future climate (2021 - 2050). A delay in rest completion of about 10-20 days has been predicted for future climate for most of the cultivars. On the other hand the predicted rise in air temperature causes an earlier development of

  4. Effect of variable thermal conductivity and specific heat capacity on the calculation of the critical metal hydride thickness for Ti1.1CrMn

    DEFF Research Database (Denmark)

    Mazzucco, Andrea; Rokni, Masoud

    2014-01-01

    model is applied to the metal hydride system, with Ti 1.1 CrMn as the absorbing alloy, to predict the weight fraction of absorbed hydrogen and solid bed temperat ure . Dependencies of thermal conductivity and specific heat capacity upon pressure and hydrogen content respectively , are accounted for...

  5. Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Miao Wang

    2017-05-01

    Full Text Available Dengue virus (DENV co-circulates as four serotypes (DENV1-4. Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS. Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR, a process known as antibody dependent enhancement (ADE. Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM of DENV. However, there is still no effective drugs or vaccines to prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human sera (anti-DENV-2 and DENV-2 prM monoclonal antibody (prM mAb could significantly enhance DENV-1 infection in K562 cells. Then we developed anti-idiotypic antibodies (prM-AIDs specific to prM mAb by immunizing of Balb/c mice. Results showed that these polyclonal antibodies can dramatically reduce ADE phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE effect of prM-AIDs in vivo, interferon-α and γ receptor-deficient mice (AG6 were used as the mouse model for DENV infection. We found that administration of DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10 (IL-10 and alaninea minotransferase (ALT in mice infected with DENV-1, similar to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative control level. Of note, the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group. These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo, suggested that anti-idiotypic antibodies might be a new choice to be considered to

  6. Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection.

    Science.gov (United States)

    Wang, Miao; Yang, Fan; Huang, Dana; Huang, Yalan; Zhang, Xiaomin; Wang, Chao; Zhang, Shaohua; Zhang, Renli

    2017-01-01

    Dengue virus (DENV) co-circulates as four serotypes (DENV1-4). Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody dependent enhancement (ADE). Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM) of DENV. However, there is still no effective drugs or vaccines to prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human sera (anti-DENV-2) and DENV-2 prM monoclonal antibody (prM mAb) could significantly enhance DENV-1 infection in K562 cells. Then we developed anti-idiotypic antibodies (prM-AIDs) specific to prM mAb by immunizing of Balb/c mice. Results showed that these polyclonal antibodies can dramatically reduce ADE phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE effect of prM-AIDs in vivo , interferon-α and γ receptor-deficient mice (AG6) were used as the mouse model for DENV infection. We found that administration of DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10 (IL-10) and alaninea minotransferase (ALT) in mice infected with DENV-1, similar to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative control level. Of note, the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group. These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo , suggested that anti-idiotypic antibodies might be a new choice to be considered to treat

  7. The protection motivation theory within the stages of the transtheoretical model - stage-specific interplay of variables and prediction of exercise stage transitions.

    Science.gov (United States)

    Lippke, Sonia; Plotnikoff, Ronald C

    2009-05-01

    Two different theories of health behaviour have been chosen with the aim of theory integration: a continuous theory (protection motivation theory, PMT) and a stage model (transtheoretical model, TTM). This is the first study to test whether the stages of the TTM moderate the interrelation of PMT-variables and the mediation of motivation, as well as PMT-variables' interactions in predicting stage transitions. Hypotheses were tested regarding (1) mean patterns, stage pair-comparisons and nonlinear trends using ANOVAs; (2) prediction-patterns for the different stage groups employing multi-group structural equation modelling (MSEM) and nested model analyses; and (3) stage transitions using binary logistic regression analyses. Adults (N=1,602) were assessed over a 6 month period on their physical activity stages, PMT-variables and subsequent behaviour. (1) Particular mean differences and nonlinear trends in all test variables were found. (2) The PMT adequately fitted the five stage groups. The MSEM revealed that covariances within threat appraisal and coping appraisal were invariant and all other constrains were stage-specific, i.e. stage was a moderator. Except for self-efficacy, motivation fully mediated the relationship between the social-cognitive variables and behaviour. (3) Predicting stage transitions with the PMT-variables underscored the importance of self-efficacy. Only when threat appraisal and coping appraisal were high, stage movement was more likely in the preparation stage. Results emphasize stage-specific differences of the PMT mechanisms, and hence, support the stage construct. The findings may guide further theory building and research integrating different theoretical approaches.

  8. Sensitivity, specificity and predictive values of linear and nonlinear indices of heart rate variability in stable angina patients

    Directory of Open Access Journals (Sweden)

    Pivatelli Flávio

    2012-10-01

    Full Text Available Abstract Background Decreased heart rate variability (HRV is related to higher morbidity and mortality. In this study we evaluated the linear and nonlinear indices of the HRV in stable angina patients submitted to coronary angiography. Methods We studied 77 unselected patients for elective coronary angiography, which were divided into two groups: coronary artery disease (CAD and non-CAD groups. For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 40 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal], NN50 [total number of adjacent RR intervals with a difference of duration greater than 50ms] and RMSSD [root-mean square of differences] and frequency domains ultra-low frequency (ULF ≤ 0,003 Hz, very low frequency (VLF 0,003 – 0,04 Hz, low frequency (LF (0.04–0.15 Hz, and high frequency (HF (0.15–0.40 Hz as well as the ratio between LF and HF components (LF/HF. In relation to the nonlinear indices we evaluated SD1, SD2, SD1/SD2, approximate entropy (−ApEn, α1, α2, Lyapunov Exponent, Hurst Exponent, autocorrelation and dimension correlation. The definition of the cutoff point of the variables for predictive tests was obtained by the Receiver Operating Characteristic curve (ROC. The area under the ROC curve was calculated by the extended trapezoidal rule, assuming as relevant areas under the curve ≥ 0.650. Results Coronary arterial disease patients presented reduced values of SDNN, RMSSD, NN50, HF, SD1, SD2 and -ApEn. HF ≤ 66 ms2, RMSSD ≤ 23.9 ms, ApEn ≤−0.296 and NN50 ≤ 16 presented the best discriminatory power for the presence of significant coronary obstruction. Conclusion We suggest the use of Heart Rate Variability Analysis in linear and nonlinear domains, for prognostic purposes in patients with stable angina pectoris, in view of their overall impairment.

  9. Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation.

    Science.gov (United States)

    Dorado, Beatriz; Area, Estela; Akman, Hasan O; Hirano, Michio

    2011-01-01

    Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion. To determine the bases of disease onset, organ specificity and severity of TK2 deficiency, we have carefully characterized Tk2 H126N knockin mice (Tk2-/-). Although normal until postnatal day 8, Tk2-/- mice rapidly develop fatal encephalomyopathy between postnatal days 10 and 13. We have observed that wild-type Tk2 activity is constant in the second week of life, while Tk1 activity decreases significantly between postnatal days 8 and 13. The down-regulation of Tk1 activity unmasks Tk2 deficiency in Tk2-/- mice and correlates with the onset of mtDNA depletion in the brain and the heart. Resistance to pathology in Tk2 mutant organs depends on compensatory mechanisms to the reduced mtDNA level. Our analyses at postnatal day 13 have revealed that Tk2-/- heart significantly increases mitochondrial transcript levels relative to the mtDNA content. This transcriptional compensation allows the heart to maintain normal levels of mtDNA-encoded proteins. The up-regulation in mitochondrial transcripts is not due to increased expression of the master mitochondrial biogenesis regulators peroxisome proliferator-activated receptor-gamma coactivator 1 alpha and nuclear respiratory factors 1 and 2, or to enhanced expression of the mitochondrial transcription factors A, B1 or B2. Instead, Tk2-/- heart compensates for mtDNA depletion by down-regulating the expression of the mitochondrial transcriptional terminator transcription factor 3 (MTERF3). Understanding the molecular mechanisms that allow Tk2 mutant organs to be spared may help design therapies for Tk2 deficiency.

  10. Lactate promotes specific differentiation in bovine granulosa cells depending on lactate uptake thus mimicking an early post-LH stage

    Directory of Open Access Journals (Sweden)

    Anja Baufeld

    2018-02-01

    Full Text Available Abstract Background The LH-induced folliculo-luteal transformation is connected with alterations of the gene expression profile in cells of the granulosa layer. It has been described that hypoxic conditions occur during luteinization, thus favoring the formation of L-lactate within the follicle. Despite being a product of anaerobic respiration, L-lactate has been shown to act as a signaling molecule affecting gene expression in neuronal cells. During the present study, we tested the hypothesis that L-lactate may influence differentiation of follicular granulosa cells (GC. Methods In a bovine granulosa cell culture model effects of L- and D-lactate, of increased glucose concentrations and of the lactate transport inhibitor UK5099 were analyzed. Steroid hormone production was analyzed by RIA and the abundance of key transcripts was determined by quantitative real-time RT-PCR. Results L-lactate decreased the production of estradiol and significantly affected selected genes of the folliculo-luteal transition as well as genes of the lactate metabolism. CYP19A1, FSHR, LHCGR were down-regulated, whereas RGS2, VNN2, PTX3, LDHA and lactate transporters were up-regulated. These effects could be partly or completely reversed by pre-treatment of the cells with UK5099. The non-metabolized enantiomer D-lactate had even more pronounced effects on gene expression, whereas increased glucose concentrations did not affect transcript abundance. Conclusions In summary, our data suggest that L-lactate specifically alters physiological and molecular characteristics of GC. These effects critically depend on L-lactate uptake, but are not triggered by increased energy supply. Further, we could show that L-lactate has a positive feedback on the lactate metabolism. Therefore, we hypothesize that L-lactate acts as a signaling molecule in bovine and possibly other monovular species supporting differentiation during the folliculo-luteal transformation.

  11. General and Specific Contributions of RAN to Reading and Arithmetic Fluency in First Graders: A Longitudinal Latent Variable Approach

    Directory of Open Access Journals (Sweden)

    Caroline Hornung

    2017-10-01

    Full Text Available In the present study, we opted for a longitudinal design and examined rapid automatized naming (RAN performance from two perspectives. In a first step, we examined the structure of RAN performance from a general cognitive perspective. We investigated whether rapid naming measures (e.g., digit RAN and color RAN reflect a mainly domain-general factor or domain-specific factors. In a second step, we examined how the best fitting RAN model was related to reading and arithmetic outcomes, assessed several months later. Finally in a third step we took a clinical perspective and investigated specific contributions of RAN measures to reading and arithmetic outcomes. While RAN has emerged as a promising predictor of reading, the relationship between RAN and arithmetic has been less examined in the past. Hundred and twenty-two first graders completed seven RAN tasks, each comprising visually familiar stimuli such as digits, vowels, consonants, dice, finger-numeral configurations, objects, and colors. Four months later the same children completed a range of reading and arithmetic tasks. From a general descriptive perspective, structural equation modeling supports a one-dimensional RAN factor in 6- to -7-year-old children. However, from a clinical perspective, our findings emphasize the specific contributions of RANs. Interestingly, alphanumeric RANs (i.e., vowel RAN were most promising when predicting reading skills and number-specific RANs (i.e., finger-numeral configuration RAN were most promising when predicting arithmetic fluency. The implications for clinical and educational practices will be discussed.

  12. General and Specific Contributions of RAN to Reading and Arithmetic Fluency in First Graders: A Longitudinal Latent Variable Approach

    OpenAIRE

    Caroline Hornung; Romain Martin; Michel Fayol; Michel Fayol

    2017-01-01

    In the present study, we opted for a longitudinal design and examined rapid automatized naming (RAN) performance from two perspectives. In a first step, we examined the structure of RAN performance from a general cognitive perspective. We investigated whether rapid naming measures (e.g., digit RAN and color RAN) reflect a mainly domain-general factor or domain-specific factors. In a second step, we examined how the best fitting RAN model was related to reading and arithmetic outcomes, assesse...

  13. Optimization of operating variables for production of ultra-fine talc in a stirred mill. Specific surface area investigations

    Directory of Open Access Journals (Sweden)

    Toraman Oner Yusuf

    2016-01-01

    Full Text Available Due to its properties such as chemical inertness, softness, whiteness, high thermal conductivity, low electrical conductivity and adsorption properties talc has wide industrial applications in paper, cosmetics, paints, polymer, ceramics, refractory materials and pharmaceutical. The demand for ultra-fine talc is emerging which drives the mineral industry to produce value added products. In this study, it was investigated how certain grinding parameters such as mill speed, ball filling ratio, powder filling ratio and grinding time of dry stirred mill affect grindability of talc ore (d97=127 μm. A series of laboratory experiments using a 24 full factorial design was conducted to determine the optimal operational parameters of a stirred mill in order to minimize the specific surface area. The main and interaction effects on the volume specific surface area (SV, m2.cm−3 of the ground product were evaluated using the Yates analysis. Under the optimal conditions at the stirrer speed of 600 rpm, grinding time of 20 min, sample mass of 5% and ball ratio of 70%, the resulting talc powder had larger volume specific surface area (i.e., 3.48 m2.cm−3 than the starting material (i.e., 1.84 m2.cm−3.

  14. Age-Specific And Sexual Variability Of Morphological And Biomechanical Parameters Of Anterior Cerebral Artery Of Adults

    Directory of Open Access Journals (Sweden)

    I.V. Kirillova

    2009-12-01

    Full Text Available In the experiment on monoaxonic longitudinal distension by tensile-testing machine Tira Test 28005 (Germany with loading unit - 100 N the general rigidity, breaking point and relative lengthening of anterior cerebral artery (АСА of adult people have been under study. Under the microscope on transverse sections the external diameter of the artery, its wall thickness have been measured and diameter of lumen have been calculated. In total 228 АСА (132 - from corpses of men, 92-from corpses of women have been investigated. They have been received in 16 hours after autopsy of adult people whose cause of death has not been connected with vascular cerebral pathology. It has been revealed that right АСА is longer and narrower than left one. ACA's wall length and thickness predominate in men in comparison with women in average of 5,4 - 13,0%. With years АСА lengthens, its external diameter increases. Biomechanical parameters of ACA's wall do not have any authentic sexual differences, they don't depend on the side of the arterial ring. With years the rigidity of АСА decreases, especially in middle age. In old age its general rigidity increases. It is connected with the increase of ACA's wall thickness. The ability of АСА to lengthening doesn't depend upon age. Experimental findings may be used as criteria of age standard of morphological and biomechanical parameters of АСА

  15. Heterogeneity of soil surface ammonium concentration and other characteristics, related to plant specific variability in a Mediterranean-type ecosystem

    International Nuclear Information System (INIS)

    Cruz, Cristina; Bio, Ana M.F.; Jullioti, Aldo; Tavares, Alice; Dias, Teresa; Martins-Loucao, Maria Amelia

    2008-01-01

    Heterogeneity and dynamics of eight soil surface characteristics essential for plants-ammonium and nitrate concentrations, water content, temperature, pH, organic matter, nitrification and ammonification rates-were studied in a Mediterranean-type ecosystem on four occasions over a year. Soil properties varied seasonally and were influenced by plant species. Nitrate and ammonium were present in the soil at similar concentrations throughout the year. The positive correlation between them at the time of greatest plant development indicates that ammonium is a readily available nitrogen source in Mediterranean-type ecosystems. The results presented here suggest that plant cover significantly affects soil surface characteristics. - In Mediterranean-type ecosystems ammonium is present in the soil throughout the year and its concentration is dependent on plant cover

  16. Protection against syphilis correlates with specificity of antibodies to the variable regions of Treponema pallidum repeat protein K.

    Science.gov (United States)

    Morgan, Cecilia A; Lukehart, Sheila A; Van Voorhis, Wesley C

    2003-10-01

    Syphilis has been recognized as a disease since the late 1400s, yet there is no practical vaccine available. One impediment to the development of a vaccine is the lack of understanding of multiple reinfections in humans despite the development of robust immune responses during the first episode. It has been shown that the Treponema pallidum repeat protein K (TprK) differs in seven discrete variable (V) regions in isolates and that the antibody response during infection is directed to these V regions. Immunization with TprK confers significant protection against infection with the homologous strain. We hypothesize that the antigenic diversity of TprK is involved in immune evasion, which contributes to the lack of heterologous protection. Here, using the rabbit model, we show a correlation between limited heterologous protection and tprK diversity in the challenge inoculum. We demonstrate that antibody responses to the V regions of one TprK molecule show limited cross-reactivity with heterologous TprK V regions.

  17. Optimization of the Method of Active Ingredients Adding to the Base of Medicinal Films Depending on Certain Variables

    Directory of Open Access Journals (Sweden)

    L. L. Davtian

    2018-03-01

    Full Text Available The influence of variables of pharmaceutical factors on the technological processes of drugs manufacturing is incredibly important. Thus, in the development of a new drug in the form of medicinal films, the relevance and necessity of determining the effect of the methods of active substances adding on the effectiveness of the drug was determined. The aim is rationalization of the method of the active pharmaceutical ingredients adding into the composition of the developed drug. Materials and methods. As experimental samples we used medicinal films, which were made using various methods of active ingredients adding. The quality of the samples was evaluated by the antimicrobial activity against Clostridium sporogenes and Staphylococcus aureus, which was determined by the diffusion method in agar. Results. The study of the antimicrobial activity of medicinal films with various methods of active ingredients adding showed that the adding of metronidazole as an aqueous solution increases the antimicrobial activity of the films by 21.23%, 16.89%, 28.59%, respectively, compared with films of similar composition, in which metronidazole was added as a suspension, and the remaining ingredients were added by the same way. The introduction of chlorhexidine bigluconate and glucosamine hydrochloride in the film-forming solution lastly together with the solution of metronidazole increases the antimicrobial activity by 24.67%, which is probably due to the absence of contact between thermolabile ingredients and solutions of film-forming substances having a high dissolution temperature. Conclusions. The most rational is adding of metronidazole to the medicinal films in the form of a 0.01% aqueous solution in a mixture with the chlorhexidine bigluconate and glucosamine hydrochloride solution to the final film-forming solution.

  18. Intraspecies Variability Affects Heterotypic Biofilms of Porphyromonas gingivalis and Prevotella intermedia: Evidences of Strain-Dependence Biofilm Modulation by Physical Contact and by Released Soluble Factors.

    Directory of Open Access Journals (Sweden)

    Graziela Murta Barbosa

    Full Text Available It is well known that strain and virulence diversity exist within the population structure of Porphyromonas gingivalis. In the present study we investigate intra- and inter-species variability in biofilm formation of Porphyromonas gingivalis and partners Prevotella intermedia and Prevotella nigrescens. All strains tested showed similar hydrophobicity, except for P. gingivalis W83 which has roughly half of the hydrophobicity of P. gingivalis ATCC33277. An intraspecies variability in coaggregation of P. gingivalis with P. intermedia was also found. The association P. gingivalis W83/P. intermedia 17 produced the thickest biofilm and strain 17 was prevalent. In a two-compartment system P. gingivalis W83 stimulates an increase in biomass of strain 17 and the latter did not stimulate the growth of P. gingivalis W83. In addition, P. gingivalis W83 also stimulates the growth of P. intermedia ATCC25611 although strain W83 was prevalent in the association with P. intermedia ATCC25611. P. gingivalis ATCC33277 was prevalent in both associations with P. intermedia and both strains of P. intermedia stimulate the growth of P. gingivalis ATCC33277. FISH images also showed variability in biofilm structure. Thus, the outcome of the association P. gingivalis/P. intermedia seems to be strain-dependent, and both soluble factors and physical contact are relevant. The association P. gingivalis-P. nigrescens ATCC33563 produced larger biomass than each monotypic biofilm, and P. gingivalis was favored in consortia, while no differences were found in the two-compartment system. Therefore, in consortia P. gingivalis-P. nigrescens physical contact seems to favor P. gingivalis growth. The intraspecies variability found in our study suggests strain-dependence in ability of microorganisms to recognize molecules in other bacteria which may further elucidate the dysbiosis event during periodontitis development giving additional explanation for periodontal bacteria, such as P

  19. Intraspecies Variability Affects Heterotypic Biofilms of Porphyromonas gingivalis and Prevotella intermedia: Evidences of Strain-Dependence Biofilm Modulation by Physical Contact and by Released Soluble Factors.

    Science.gov (United States)

    Barbosa, Graziela Murta; Colombo, Andrea Vieira; Rodrigues, Paulo Henrique; Simionato, Maria Regina Lorenzetti

    2015-01-01

    It is well known that strain and virulence diversity exist within the population structure of Porphyromonas gingivalis. In the present study we investigate intra- and inter-species variability in biofilm formation of Porphyromonas gingivalis and partners Prevotella intermedia and Prevotella nigrescens. All strains tested showed similar hydrophobicity, except for P. gingivalis W83 which has roughly half of the hydrophobicity of P. gingivalis ATCC33277. An intraspecies variability in coaggregation of P. gingivalis with P. intermedia was also found. The association P. gingivalis W83/P. intermedia 17 produced the thickest biofilm and strain 17 was prevalent. In a two-compartment system P. gingivalis W83 stimulates an increase in biomass of strain 17 and the latter did not stimulate the growth of P. gingivalis W83. In addition, P. gingivalis W83 also stimulates the growth of P. intermedia ATCC25611 although strain W83 was prevalent in the association with P. intermedia ATCC25611. P. gingivalis ATCC33277 was prevalent in both associations with P. intermedia and both strains of P. intermedia stimulate the growth of P. gingivalis ATCC33277. FISH images also showed variability in biofilm structure. Thus, the outcome of the association P. gingivalis/P. intermedia seems to be strain-dependent, and both soluble factors and physical contact are relevant. The association P. gingivalis-P. nigrescens ATCC33563 produced larger biomass than each monotypic biofilm, and P. gingivalis was favored in consortia, while no differences were found in the two-compartment system. Therefore, in consortia P. gingivalis-P. nigrescens physical contact seems to favor P. gingivalis growth. The intraspecies variability found in our study suggests strain-dependence in ability of microorganisms to recognize molecules in other bacteria which may further elucidate the dysbiosis event during periodontitis development giving additional explanation for periodontal bacteria, such as P. gingivalis and P

  20. Mosaic Expression of Thyroid Hormone Regulatory Genes Defines Cell Type-Specific Dependency in the Developing Chicken Cerebellum.

    Science.gov (United States)

    Delbaere, Joke; Van Herck, Stijn L J; Bourgeois, Nele M A; Vancamp, Pieter; Yang, Shuo; Wingate, Richard J T; Darras, Veerle M

    2016-12-01

    The cerebellum is a morphologically unique brain structure that requires thyroid hormones (THs) for the correct coordination of key cellular events driving its development. Unravelling the interplay between the multiple factors that can regulate intracellular TH levels is a key step to understanding their role in the regulation of these cellular processes. We therefore investigated the regional/cell-specific expression pattern of TH transporters and deiodinases in the cerebellum using the chicken embryo as a model. In situ hybridisation revealed expression of the TH transporters monocarboxylate transporter 8 (MCT8) and 10 (MCT10), L-type amino acid transporter 1 (LAT1) and organic anion transporting polypeptide 1C1 (OATP1C1) as well as the inactivating type 3 deiodinase (D3) in the fourth ventricle choroid plexus, suggesting a possible contribution of the resulting proteins to TH exchange and subsequent inactivation of excess hormone at the blood-cerebrospinal fluid barrier. Exclusive expression of LAT1 and the activating type 2 deiodinase (D2) mRNA was found at the level of the blood-brain barrier, suggesting a concerted function for LAT1 and D2 in the direct access of active T 3 to the developing cerebellum via the capillary endothelial cells. The presence of MCT8 mRNA in Purkinje cells and cerebellar nuclei during the first 2 weeks of embryonic development points to a potential role of this transporter in the uptake of T 3 in central neurons. At later stages, together with MCT10, detection of MCT8 signal in close association with the Purkinje cell dendritic tree suggests a role of both transporters in TH signalling during Purkinje cell synaptogenesis. MCT10 was also expressed in late-born cells in the rhombic lip lineage with a clear hybridisation signal in the outer external granular layer, indicating a potential role for MCT10 in the proliferation of granule cell precursors. By contrast, expression of D3 in the first-born rhombic lip-derived population may

  1. Inter- and intra-specific variability in δ13C and δ18O values of freshwater gastropod shells from Lake Lednica, western Poland

    Science.gov (United States)

    Apolinarska, Karina; Pełechaty, Mariusz

    2017-09-01

    This study focuses on the inter- and intra-specific variability in δ13C and δ18O values of shells and opercula of gastropods sampled live from the littoral zone of Lake Lednica, western Poland. The δ13C and δ18O values were measured in individual opercula of Bithynia tentaculata and in shells of Bithynia tentaculata, Gyraulus albus, Gyraulus crista, Lymnaea sp., Physa fontinalis, Radix auricularia, Theodoxus fluviatilis and Valvata cristata. The gastropods selected for the study are among the species most commonly found in European Quaternary lacustrine sediments. The carbon isotope composition of the gastropod shells was species-specific and the same order of species from the most to the least 13C-depleted was observed at all sites sampled. Differences in shell δ13C values between species were similar at all sampling sites, thus the factors influencing shell isotopic composition were interpreted as species-specific. The δ18O values of shells were similar in all the species investigated. Significant intra-specific variability in shell δ13C and δ18O values was observed not only within the populations of Lake Lednica, which can be explained by heterogeneity of δ13C DIC, δ18O water and water temperature between the sites where macrophytes with snails attached were sampled, but also between individuals sampled from restricted areas of the lake's bottom. The latter points to the importance of factors related to the ontogeny of individual gastropods.

  2. Systematic spatial bias in DNA microarray hybridization is caused by probe spot position-dependent variability in lateral diffusion.

    Science.gov (United States)

    Steger, Doris; Berry, David; Haider, Susanne; Horn, Matthias; Wagner, Michael; Stocker, Roman; Loy, Alexander

    2011-01-01

    The hybridization of nucleic acid targets with surface-immobilized probes is a widely used assay for the parallel detection of multiple targets in medical and biological research. Despite its widespread application, DNA microarray technology still suffers from several biases and lack of reproducibility, stemming in part from an incomplete understanding of the processes governing surface hybridization. In particular, non-random spatial variations within individual microarray hybridizations are often observed, but the mechanisms underpinning this positional bias remain incompletely explained. This study identifies and rationalizes a systematic spatial bias in the intensity of surface hybridization, characterized by markedly increased signal intensity of spots located at the boundaries of the spotted areas of the microarray slide. Combining observations from a simplified single-probe block array format with predictions from a mathematical model, the mechanism responsible for this bias is found to be a position-dependent variation in lateral diffusion of target molecules. Numerical simulations reveal a strong influence of microarray well geometry on the spatial bias. Reciprocal adjustment of the size of the microarray hybridization chamber to the area of surface-bound probes is a simple and effective measure to minimize or eliminate the diffusion-based bias, resulting in increased uniformity and accuracy of quantitative DNA microarray hybridization.

  3. Variability of the 2014-present inflation source at Mauna Loa volcano revealed using time-dependent modeling

    Science.gov (United States)

    Johanson, I. A.; Miklius, A.; Okubo, P.; Montgomery-Brown, E. K.

    2017-12-01

    Mauna Loa volcano is the largest active volcano on earth and in the 20thcentury produced roughly one eruption every seven years. The 33-year quiescence since its last eruption 1984 has been punctuated by three inflation episodes where magma likely entered the shallow plumbing system, but was not erupted. The most recent began in 2014 and is ongoing. Unlike prior inflation episodes, the current one is accompanied by a significant increase in shallow seismicity, a pattern that is similar to earlier pre-eruptive periods. We apply the Kalman filter based Network Inversion Filter (NIF) to the 2014-present inflation episode using data from a 27 station continuous GPS network on Mauna Loa. The model geometry consists of a point volume source and tabular, dike-like body, which have previously been shown to provide a good fit to deformation data from a 2004-2009 inflation episode. The tabular body is discretized into 1km x 1km segments. For each day, the NIF solves for the rates of opening on the tabular body segments (subject to smoothing and positivity constraints), volume change rate in the point source, and slip rate on a deep décollement fault surface, which is constrained to a constant (no transient slip allowed). The Kalman filter in the NIF provides for smoothing both forwards and backwards in time. The model shows that the 2014-present inflation episode occurred as several sub-events, rather than steady inflation. It shows some spatial variability in the location of the inflation sub-events. In the model, opening in the tabular body is initially concentrated below the volcano's summit, in an area roughly outlined by shallow seismicity. In October, 2015 opening in the tabular body shifts to be centered beneath the southwest portion of the summit and seismicity becomes concentrated in this area. By late 2016, the opening rate on the tabular body decreases and is once again under the central part of summit. This modeling approach has allowed us to track these

  4. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

    Science.gov (United States)

    Lu, Chenggang; Fuller, Margaret T

    2015-12-01

    Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages.

  5. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

    Directory of Open Access Journals (Sweden)

    Chenggang Lu

    2015-12-01

    Full Text Available Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s. In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC, a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs, spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages.

  6. Immortalisation with hTERT Impacts on Sulphated Glycosaminoglycan Secretion and Immunophenotype in a Variable and Cell Specific Manner.

    Directory of Open Access Journals (Sweden)

    Tina P Dale

    differentiation potential, was affected in a variable manner. As such, these cells are not a direct substitute for primary cells in cartilage regeneration research.

  7. JTC801 Induces pH-dependent Death Specifically in Cancer Cells and Slows Growth of Tumors in Mice.

    Science.gov (United States)

    Song, Xinxin; Zhu, Shan; Xie, Yangchun; Liu, Jiao; Sun, Lingyi; Zeng, Dexing; Wang, Pengcheng; Ma, Xiaochao; Kroemer, Guido; Bartlett, David L; Billiar, Timothy R; Lotze, Michael T; Zeh, Herbert J; Kang, Rui; Tang, Daolin

    2018-04-01

    lineage kinase domain like pseudokinase [MLKL]), or ferroptosis (degradation of glutathione peroxidase 4 [GPX4]). Inhibitors of apoptosis (Z-VAD-FMK), necroptosis (necrosulfonamide), ferroptosis (ferrostatin-1), or autophagy (hydroxychloroquine) did not prevent JTC801-induced death of PANC1 or MiaPaCa2 cells. The cytotoxic effects of JTC801 in immortalized fibroblast cell lines was not affected by disruption of genes that promote apoptosis (Bax -/- /Bak -/- cells), necroptosis (Ripk1 -/- , Ripk3 -/- , or Mlkl -/- cells), ferroptosis (Gpx4 -/- cells), or autophagy (Atg3 -/- , Atg5 -/- , Atg7 -/- , or Sqstm1 -/- cells). We found JTC801 to induce a pH-dependent form cell death (alkaliptosis) in cancer cells but not normal cells (hepatocytes, bone marrow CD34 + progenitor cells, peripheral blood mononuclear cells, or dermal fibroblasts) or healthy tissues of C57BL/6 mice. JTC801 induced alkaliptosis in cancer cells by activating NF-κB, which repressed expression of the carbonic anhydrase 9 gene (CA9), whose product regulates pH balance in cells. In analyses of Cancer Genome Atlas data and tissue microarrays, we associated increased tumor level of CA9 mRNA or protein with shorter survival times of patients with pancreatic, kidney, or lung cancers. Knockdown of CA9 reduced the protective effects of NF-κB inhibition on JTC801-induced cell death and intracellular alkalinization in PANC1 and MiaPaCa2 cell lines. Oral administration of JTC801 inhibited growth of xenograft tumors (from PANC1, MiaPaCa2, SK-MEL-28, PC-3, 786-0, SF-295, HCT116, OV-CAR3, and HuH7 cells), orthotropic tumors (from KPC cells), lung metastases (from KPC cells) of mice, and slowed growth of tumors in KCH mice. In a screen of agents that interact with GPCR pathways, we found JTC801 to induce pH-dependent cell death (alkaliptosis) specifically in cancer cells such as PDAC cells, by reducing expression of CA9. Levels of CA9 are increased in human cancer tissues. JTC801 might be developed for treatment of

  8. The influence of endophenotypic, disease-specific, and environmental variables on the expression of anxiety in pediatric epilepsy.

    Science.gov (United States)

    Schraegle, William A; Titus, Jeffrey B

    2017-10-01

    Children and adolescents with epilepsy often show higher rates of anxiety, which carries an increased risk for reduced health-related quality of life (HRQOL). The current study assessed the role of parental psychiatric history (i.e., anxiety, depression, and/or bipolar disorder) on the rate of anxiety features in youth seen in a tertiary epilepsy clinic. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 180 children and adolescents (mean age=11.40, SD=3.98). Our results identified clinically elevated anxiety ratings in nearly half the sample (47%) with previous psychiatric history endorsed by 48% of parents. The effect of parental psychiatric history on youth anxiety was found to be significant and associated with a threefold increase in the rate of youth anxiety features. This risk increased to fourfold in refractory epilepsy, and the impact of family psychiatric history is greater in adolescent females and in families that report higher levels of stress. In those families who reported no psychiatric history, anxiety was best predicted by epilepsy-specific factors above and beyond sociodemographic factors. Parental psychiatric history was also identified as a significant risk factor for diminished patient HRQOL, even after accounting for seizure control. These findings highlight the impact of family and epilepsy factors on psychological functioning and offer further support for the strong relationship between parental adjustment and child outcome in pediatric epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Sex- and limb-specific differences in the nitric oxide-dependent cutaneous vasodilation in response to local heating

    Science.gov (United States)

    Stanhewicz, Anna E.; Greaney, Jody L.; Larry Kenney, W.

    2014-01-01

    Local heating of the skin is commonly used to assess cutaneous microvasculature function. Controversy exists as to whether there are limb or sex differences in the nitric oxide (NO)-dependent contribution to this vasodilation, as well as the NO synthase (NOS) isoform mediating the responses. We tested the hypotheses that 1) NO-dependent vasodilation would be greater in the calf compared with the forearm; 2) total NO-dependent dilation would not be different between sexes within limb; and 3) women would exhibit greater neuronal NOS (nNOS)-dependent vasodilation in the calf. Two microdialysis fibers were placed in the skin of the ventral forearm and the calf of 19 (10 male and 9 female) young (23 ± 1 yr) adults for the local delivery of Ringer solution (control) or 5 mM Nω-propyl-l-arginine (NPLA; nNOS inhibition). Vasodilation was induced by local heating (42°C) at each site, after which 20 mM NG-nitro-l-arginine methyl ester (l-NAME) was perfused for within-site assessment of NO-dependent vasodilation. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial pressure and normalized to maximum (28 mM sodium nitroprusside, 43°C). Total NO-dependent vasodilation in the calf was lower compared with the forearm in both sexes (Ringer: 42 ± 5 vs. 62 ± 4%; P 0.05). These data suggest that the NO-dependent component of local heating-induced cutaneous vasodilation is lower in the calf compared with the forearm. Contrary to our original hypothesis, there was no contribution of nNOS to NO-dependent vasodilation in either limb during local heating. PMID:25100074

  10. A variable-order time-dependent neutron transport method for nuclear reactor kinetics using analytically-integrated space-time characteristics

    International Nuclear Information System (INIS)

    Hoffman, A. J.; Lee, J. C.

    2013-01-01

    A new time-dependent neutron transport method based on the method of characteristics (MOC) has been developed. Whereas most spatial kinetics methods treat time dependence through temporal discretization, this new method treats time dependence by defining the characteristics to span space and time. In this implementation regions are defined in space-time where the thickness of the region in time fulfills an analogous role to the time step in discretized methods. The time dependence of the local source is approximated using a truncated Taylor series expansion with high order derivatives approximated using backward differences, permitting the solution of the resulting space-time characteristic equation. To avoid a drastic increase in computational expense and memory requirements due to solving many discrete characteristics in the space-time planes, the temporal variation of the boundary source is similarly approximated. This allows the characteristics in the space-time plane to be represented analytically rather than discretely, resulting in an algorithm comparable in implementation and expense to one that arises from conventional time integration techniques. Furthermore, by defining the boundary flux time derivative in terms of the preceding local source time derivative and boundary flux time derivative, the need to store angularly-dependent data is avoided without approximating the angular dependence of the angular flux time derivative. The accuracy of this method is assessed through implementation in the neutron transport code DeCART. The method is employed with variable-order local source representation to model a TWIGL transient. The results demonstrate that this method is accurate and more efficient than the discretized method. (authors)

  11. Non-adjacent dependency learning in Cantonese-speaking\\ud children with and without a history of specific language\\ud impairment

    OpenAIRE

    Iao, L-S; Ng, LY; Wong, AMY; Lee, OT

    2017-01-01

    Purpose: This study investigated non-adjacent dependency learning in Cantonese-speaking children with and without a history of Specific Language Impairment (SLI) in an artificial linguistic context.\\ud \\ud Method: Sixteen Cantonese-speaking children with SLI history and 16 Cantonese-speaking children with typical language development (TLD) were tested with a non-adjacent dependency learning task using artificial languages that mimic Cantonese.\\ud \\ud Results: Children with TLD performed above...

  12. Analysis of arterial pressure variability in patients with acute cerebral stroke depending on the time of occurrence

    Directory of Open Access Journals (Sweden)

    Volosovets A.O.

    2017-12-01

    Full Text Available Arterial hypertension can cause a pronounced negative influence on the state of the cerebral vascular system and lead to significant microtraumatization of the walls of the vessels and disruption of vascular autoregulation. This predictor has the greatest influence on the onset of ischemic stroke of atherothrombotic and lacunar subtypes, however, hypertension occurs almost in all patients with acute cerebral ischemia. Interesting and not at all presented in modern scientific literature is the question of the relationship of oscillation of blood pressure with the period of the onset of the focus of ischemia, which predetermined the purpose of our work. The purpose of our study was to determine the relationship between deformation of the profile of fluctuations in blood pressure of patients in the acute period of ischemic stroke, depending on the time of the occurrence of cerebrovascular accident. We examined 300 patients who suffered acute ischemic stroke (men - 196, women - 104 aged 42 to 84 years (average age - 65.2 ± 8.7 years. All patients were divided into 3 groups according to the period of the day when an ischemic stroke occurred: 1 group (n=146, patients suffering from cerebral ischemia during the day (8.00-14.59; In group 2 (n=107, patients stroke was observed in the evening (15.00-21.59; Group 3 (n=47, patients had an ischemic stroke at night (22.00-7.59. For the 1st group of patients who have had ischemic stroke during the day and as a rule with an increase in blood pressure, a marked increase in blood pressure was at 12.00 and 15.00 and a tendency towards compensatory parasympathetic effect in the form of blood pressure decrease at night (over-dipper was typical. At the same time, in the 2nd group of patients with stroke in the evening, elevated blood pressure at 18.00 and 21.00 and parasympathetic activity disorders with prevalence of insufficient reduction of blood pressure in the evening and during sleep (non-dipper was observed

  13. Unbiased proteomics analysis demonstrates significant variability in mucosal immune factor expression depending on the site and method of collection.

    Directory of Open Access Journals (Sweden)

    Kenzie M Birse

    Full Text Available Female genital tract secretions are commonly sampled by lavage of the ectocervix and vaginal vault or via a sponge inserted into the endocervix for evaluating inflammation status and immune factors critical for HIV microbicide and vaccine studies. This study uses a proteomics approach to comprehensively compare the efficacy of these methods, which sample from different compartments of the female genital tract, for the collection of immune factors. Matching sponge and lavage samples were collected from 10 healthy women and were analyzed by tandem mass spectrometry. Data was analyzed by a combination of differential protein expression analysis, hierarchical clustering and pathway analysis. Of the 385 proteins identified, endocervical sponge samples collected nearly twice as many unique proteins as cervicovaginal lavage (111 vs. 61 with 55% of proteins common to both (213. Each method/site identified 73 unique proteins that have roles in host immunity according to their gene ontology. Sponge samples enriched for specific inflammation pathways including acute phase response proteins (p = 3.37×10(-24 and LXR/RXR immune activation pathways (p = 8.82×10(-22 while the role IL-17A in psoriasis pathway (p = 5.98×10(-4 and the complement system pathway (p = 3.91×10(-3 were enriched in lavage samples. Many host defense factors were differentially enriched (p<0.05 between sites including known/potential antimicrobial factors (n = 21, S100 proteins (n = 9, and immune regulatory factors such as serpins (n = 7. Immunoglobulins (n = 6 were collected at comparable levels in abundance in each site although 25% of those identified were unique to sponge samples. This study demonstrates significant differences in types and quantities of immune factors and inflammation pathways collected by each sampling technique. Therefore, clinical studies that measure mucosal immune activation or factors assessing HIV transmission should utilize

  14. Meteorological variables affect fertility rate after intrauterine artificial insemination in sheep in a seasonal-dependent manner: a 7-year study

    Science.gov (United States)

    Palacios, C.; Abecia, J. A.

    2015-05-01

    A total number of 48,088 artificial inseminations (AIs) have been controlled during seven consecutive years in 79 dairy sheep Spanish farms (41° N). Mean, maximum and minimum ambient temperatures ( Ts), temperature amplitude (TA), mean relative humidity (RH), mean solar radiation (SR) and total rainfall of each insemination day and 15 days later were recorded. Temperature-humidity index (THI) and effective temperature (ET) have been calculated. A binary logistic regression model to estimate the risk of not getting pregnant compared to getting pregnant, through the odds ratio (OR), was performed. Successful winter inseminations were carried out under higher SR ( P 1 (maximum T, ET and rainfall on AI day, and ET and rainfall on day 15), and two variables presented OR AI day and maximum T on day 15). However, the effect of meteorological factors affected fertility in opposite ways, so T becomes a protective or risk factor on fertility depending on season. In conclusion, the percentage of pregnancy after AI in sheep is significantly affected by meteorological variables in a seasonal-dependent manner, so the parameters such as temperature reverse their effects in the hot or cold seasons. A forecast of the meteorological conditions could be a useful tool when AI dates are being scheduled.

  15. First and Second-Law Efficiency Analysis and ANN Prediction of a Diesel Cycle with Internal Irreversibility, Variable Specific Heats, Heat Loss, and Friction Considerations

    Directory of Open Access Journals (Sweden)

    M. M. Rashidi

    2014-04-01

    Full Text Available The variability of specific heats, internal irreversibility, heat and frictional losses are neglected in air-standard analysis for different internal combustion engine cycles. In this paper, the performance of an air-standard Diesel cycle with considerations of internal irreversibility described by using the compression and expansion efficiencies, variable specific heats, and losses due to heat transfer and friction is investigated by using finite-time thermodynamics. Artificial neural network (ANN is proposed for predicting the thermal efficiency and power output values versus the minimum and the maximum temperatures of the cycle and also the compression ratio. Results show that the first-law efficiency and the output power reach their maximum at a critical compression ratio for specific fixed parameters. The first-law efficiency increases as the heat leakage decreases; however the heat leakage has no direct effect on the output power. The results also show that irreversibilities have depressing effects on the performance of the cycle. Finally, a comparison between the results of the thermodynamic analysis and the ANN prediction shows a maximum difference of 0.181% and 0.194% in estimating the thermal efficiency and the output power. The obtained results in this paper can be useful for evaluating and improving the performance of practical Diesel engines.

  16. Sources of variability in fatty acid (FA) biomarkers in the application of compound-specific stable isotopes (CSSIs) to soil and sediment fingerprinting and tracing: A review

    Energy Technology Data Exchange (ETDEWEB)

    Reiffarth, D.G., E-mail: Dominic.Reiffarth@unbc.ca [Natural Resources and Environmental Studies Program, University of Northern British Columbia, 3333 University Way, Prince George, BC V2N 4Z9 (Canada); Petticrew, E.L., E-mail: Ellen.Petticrew@unbc.ca [Geography Program and Quesnel River Research Centre, University of Northern British Columbia, 3333 University Way, Prince George, BC V2N 4Z9 (Canada); Owens, P.N., E-mail: Philip.Owens@unbc.ca [Environmental Science Program and Quesnel River Research Centre, University of Northern British Columbia, 3333 University Way, Prince George, BC, V2N 4Z9 (Canada); Lobb, D.A., E-mail: David.Lobb@umanitoba.ca [Watershed Systems Research Program, University of Manitoba, 13 Freedman Crescent, Winnipeg, MB R3T 2N2 (Canada)

    2016-09-15

    Determining soil redistribution and sediment budgets in watersheds is often challenging. One of the methods for making such determinations employs soil and sediment fingerprinting techniques, using sediment properties such as geochemistry, fallout radionuclides, and mineral magnetism. These methods greatly improve the estimation of erosion and deposition within a watershed, but are limited when determining land use-based soil and sediment movement. Recently, compound-specific stable isotopes (CSSIs), which employ fatty acids naturally occurring in the vegetative cover of soils, offer the possibility of refining fingerprinting techniques based on land use, complementing other methods that are currently in use. The CSSI method has been met with some success; however, challenges still remain with respect to scale and resolution due to a potentially large degree of biological, environmental and analytical uncertainty. By better understanding the source of tracers used in CSSI work and the inherent biochemical variability in those tracers, improvement in sample design and tracer selection is possible. Furthermore, an understanding of environmental and analytical factors affecting the CSSI signal will lead to refinement of the approach and the ability to generate more robust data. This review focuses on sources of biological, environmental and analytical variability in applying CSSI to soil and sediment fingerprinting, and presents recommendations based on past work and current research in this area for improving the CSSI technique. A recommendation, based on current information available in the literature, is to use very-long chain saturated fatty acids and to avoid the use of the ubiquitous saturated fatty acids, C{sub 16} and C{sub 18}. - Highlights: • Compound-specific stable isotopes (CSSIs) of carbon may be used as soil tracers. • The variables affecting CSSI data are: biological, environmental and analytical. • Understanding sources of variability will lead

  17. Sources of variability in fatty acid (FA) biomarkers in the application of compound-specific stable isotopes (CSSIs) to soil and sediment fingerprinting and tracing: A review

    International Nuclear Information System (INIS)

    Reiffarth, D.G.; Petticrew, E.L.; Owens, P.N.; Lobb, D.A.

    2016-01-01

    Determining soil redistribution and sediment budgets in watersheds is often challenging. One of the methods for making such determinations employs soil and sediment fingerprinting techniques, using sediment properties such as geochemistry, fallout radionuclides, and mineral magnetism. These methods greatly improve the estimation of erosion and deposition within a watershed, but are limited when determining land use-based soil and sediment movement. Recently, compound-specific stable isotopes (CSSIs), which employ fatty acids naturally occurring in the vegetative cover of soils, offer the possibility of refining fingerprinting techniques based on land use, complementing other methods that are currently in use. The CSSI method has been met with some success; however, challenges still remain with respect to scale and resolution due to a potentially large degree of biological, environmental and analytical uncertainty. By better understanding the source of tracers used in CSSI work and the inherent biochemical variability in those tracers, improvement in sample design and tracer selection is possible. Furthermore, an understanding of environmental and analytical factors affecting the CSSI signal will lead to refinement of the approach and the ability to generate more robust data. This review focuses on sources of biological, environmental and analytical variability in applying CSSI to soil and sediment fingerprinting, and presents recommendations based on past work and current research in this area for improving the CSSI technique. A recommendation, based on current information available in the literature, is to use very-long chain saturated fatty acids and to avoid the use of the ubiquitous saturated fatty acids, C 16 and C 18 . - Highlights: • Compound-specific stable isotopes (CSSIs) of carbon may be used as soil tracers. • The variables affecting CSSI data are: biological, environmental and analytical. • Understanding sources of variability will lead to more

  18. Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma.

    Science.gov (United States)

    Huang, T J; MacAry, P A; Eynott, P; Moussavi, A; Daniel, K C; Askenase, P W; Kemeny, D M; Chung, K F

    2001-01-01

    Th2 T cell immune-driven inflammation plays an important role in allergic asthma. We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia. OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge. Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA. Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 cells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma. Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.

  19. Presentation of valid correlations in some morphological variables and basic and specific motor skills in young people aged 13-14 years engaged in basketball

    OpenAIRE

    Miftari, Florian; Salihu, Hazir; Selimi, Musa

    2018-01-01

    Miftari Florian, Salihu Hazir, Selimi Musa. Presentation of valid correlations in some morphological variables and basic and specific motor skills in young people aged 13-14 years engaged in basketball. Journal of Education, Health and Sport. 2018;8(5):95-101. eISNN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.1242579 http://ojs.ukw.edu.pl/index.php/johs/article/view/5250 The journal has had 7 points in Ministry of Science and Higher Education pa...

  20. Intra-individual variability in the urine concentrations of inhaled salmeterol in male subjects with reference to doping analysis – impact of urine specific gravity correction

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Hemmersbach, Peter

    2012-01-01

    and a-hydroxysalmeterol during visits one and two were 12.6 and 21.8%, respectively. The intra-individual variability of salmeterol and a-hydroxysalmeterol in the urine concentrations were significantly higher when uncorrected for USG with 43.0 and 43.7% versus 20.4% (p...Since 2010, the World Anti-Doping Agency (WADA) has introduced urinary thresholds for some beta2-agonists. In doping analysis urine samples of beta2-agonists are not corrected for the Urine Specific Gravity (USG) by the WADA laboratories. Several studies have observed high differences in the urine...

  1. Brain Region-Specific Effects of cGMP-Dependent Kinase II Knockout on AMPA Receptor Trafficking and Animal Behavior

    Science.gov (United States)

    Kim, Seonil; Pick, Joseph E.; Abera, Sinedu; Khatri, Latika; Ferreira, Danielle D. P.; Sathler, Matheus F.; Morison, Sage L.; Hofmann, Franz; Ziff, Edward B.

    2016-01-01

    Phosphorylation of GluA1, a subunit of AMPA receptors (AMPARs), is critical for AMPAR synaptic trafficking and control of synaptic transmission. cGMP-dependent protein kinase II (cGKII) mediates this phosphorylation, and cGKII knockout (KO) affects GluA1 phosphorylation and alters animal behavior. Notably, GluA1 phosphorylation in the KO…

  2. p53-dependent inhibition of TrxR1 contributes to the tumor-specific induction of apoptosis by RITA.

    Science.gov (United States)

    Hedström, Elisabeth; Eriksson, Sofi; Zawacka-Pankau, Joanna; Arnér, Elias S J; Selivanova, Galina

    2009-11-01

    Thioredoxin reductase 1 (TrxR1) is a key regulator in many redox-dependent cellular pathways, and is often overexpressed in cancer. Several studies have identified TrxR1 as a potentially important target for anticancer therapy. The low molecular weight compound RITA (NSC 652287) binds p53 and induces p53-dependent apoptosis. Here we found that RITA also targets TrxR1 by non-covalent binding, followed by inhibition of its activity in vitro and by inhibition of TrxR activity in cancer cells. Interestingly, a novel approximately 130 kDa form of TrxR1, presumably representing a stable covalently linked dimer, and an increased generation of reactive oxygen species (ROS) were induced by RITA in cancer cells in a p53-dependent manner. Similarly, the gold-based TrxR inhibitor auranofin induced apoptosis related to oxidative stress, but independently of p53 and without apparent induction of the approximately 130 kDa form of TrxR1. In contrast to the effects observed in cancer cells, RITA did not inhibit TrxR or ROS formation in normal fibroblasts (NHDF). The inhibition of TrxR1 can sensitize tumor cells to agents that induce oxidative stress and may directly trigger cell death. Thus, our results suggest that a unique p53-dependent effect of RITA on TrxR1 in cancer cells might synergize with p53-dependent induction of pro-apoptotic genes and oxidative stress, thereby leading to a robust induction of cancer cell death, without affecting non-transformed cells.

  3. The redox state and the phosphorylation state of the mannitol-specific carrier of the E. coli phosphoenolpyruvate-dependent phosphotransferase system

    NARCIS (Netherlands)

    Robillard, G.T.; Pas, H.H.; Gage, D.; Elferink, M.G.L.

    1988-01-01

    This review summarizes the recent developments in identifying the activity-linked cysteine as one of the phosphorylation sites on the mannitol-specific EII of the E. coli phosphoenolpyruvate-dependent mannitol transport system. Two phosphorylation sites have been identified, one being the HPr/P-HPr

  4. Extracellular thiol-assisted selenium uptake dependent on the x(c)(-) cystine transporter explains the cancer-specific cytotoxicity of selenite

    DEFF Research Database (Denmark)

    Olm, E.; Fernandes, A. P.; Hebert, C.

    2009-01-01

    The selenium salt selenite (SeO32-) is cytotoxic in low to moderate concentrations, with a remarkable specificity for cancer cells resistant to conventional chemotherapy. Our data show that selenium uptake and accumulation, rather than intracellular events, are crucial to the specific selenite...... cytotoxicity observed in resistant cancer cells. We show that selenium uptake depends on extracellular reduction, and that the extracellular environment is a key factor specific to selenite cytotoxicity. The extracellular reduction is mediated by cysteine, and the efficacy is determined by the uptake...

  5. Dependence of the specific essential work of fracture in mode I in commercially pure copper with thickener

    International Nuclear Information System (INIS)

    Ochoa M, Herman; Monsalve G, Alberto

    2004-01-01

    Due to the great ductility of DHP copper, the classic characterization of the fracture's lineal mechanics with the critical intensity factor of K 10 tensions fails because of the increased amount of plastic deformation that the material displays before fracturing. For this reason other parameters such as the integral J are also not able to characterize the fracture phenomenon. Therefore there is a need to define a more appropriate parameter, that is able to describe the breakage phenomenon in this type of material: the specific essential work of fracture that includes the large amount of plastic deformation that can absorb materials with definite ductile behavior. Tests with DENT (Double Edge Notched Tension) pieces were carried out for the calculation of the specific essential fracture work, according to the pre-standard ESIS 1995. These tests have been carried out with pieces of different ligament lengths, so that the specific fracture energy (W sf ) correlates with the ligament length, allowing the value of the specific essential fracture work (W sf ) to be calculated. Tests have been made using pieces of different thicknesses to establish the relationship between specific essential fracture work and the thickness of the material, finding that the value of W sf increases with the increased thickness of the material (CW)

  6. Specificity of verbal learning impairment and recovery in a marijuana-dependent male: the effects of sustained marijuana abstinence

    OpenAIRE

    Vadhan, Nehal P.; van Gorp, Wilfred G.; Levin, Frances R.

    2011-01-01

    We present the case of a young adult in treatment for marijuana dependence, with recurrent depression and a history of possible TBI, complaining of concentration, memory and initiation problems. Testing at treatment baseline revealed performance that was generally in the High Average range on measures of reaction time and attention, with a selective impairment in verbal learning (Borderline to Extremely Low range). Following 8 weeks of abstinence from marijuana, his verbal learning recovered ...

  7. DNA Methylation Adjusts the Specificity of Memories Depending on the Learning Context and Promotes Relearning in Honeybees.

    Science.gov (United States)

    Biergans, Stephanie D; Claudianos, Charles; Reinhard, Judith; Galizia, C G

    2016-01-01

    The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g., associative vs. non-associative) and in what context (e.g., varying training conditions). Here, we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naïve odor and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naïve odor or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odor-coding, i.e., 'correct' (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple-trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes.

  8. 42 CFR 412.79 - Determination of the hospital-specific rate for inpatient operating costs for Medicare-dependent...

    Science.gov (United States)

    2010-10-01

    ... OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM PROSPECTIVE PAYMENT SYSTEMS FOR INPATIENT HOSPITAL SERVICES Determination of Transition Period Payment Rates for the Prospective Payment System for Inpatient... § 412.73(c)(14) through (c)(16). (e) DRG adjustment. The applicable hospital-specific cost per discharge...

  9. On the Nature and Nurture of Intelligence and Specific Cognitive Abilities: The More Heritable, the More Culture Dependent

    NARCIS (Netherlands)

    Kan, K.J.; Wicherts, J.M.; Dolan, C.V.; van der Maas, H.L.J.

    2013-01-01

    To further knowledge concerning the nature and nurture of intelligence, we scrutinized how heritability coefficients vary across specific cognitive abilities both theoretically and empirically. Data from 23 twin studies (combined N = 7,852) showed that (a) in adult samples, culture-loaded subtests

  10. On the nature and nurture of intelligence and specific cognitive abilities : The more heritable, the more culture dependent

    NARCIS (Netherlands)

    Kan, K.J.; Wicherts, J.M.; Dolan, C.; van der Maas, H.L.J.

    2013-01-01

    To further knowledge concerning the nature and nurture of intelligence, we scrutinized how heritability coefficients vary across specific cognitive abilities both theoretically and empirically. Data from 23 twin studies (combined N = 7,852) showed that (a) in adult samples, culture-loaded subtests

  11. Phase variable expression of a single phage receptor in Campylobacter jejuni NCTC12662 influences sensitivity toward several diverse CPS-dependent phages

    DEFF Research Database (Denmark)

    Gencay, Yilmaz Emre; Sørensen, Martine C.H.; Wenzel, Cory Q.

    2018-01-01

    Campylobacter jejuni NCTC12662 is sensitive to infection by many Campylobacter bacteriophages. Here we used this strain to investigate the molecular mechanism behind phage resistance development when exposed to a single phage and demonstrate how phase variable expression of one surface component...... influences phage sensitivity against many diverse C. jejuni phages. When C. jejuni NCTC12662 was exposed to phage F207 overnight, 25% of the bacterial cells were able to grow on a lawn of phage F207, suggesting that resistance develops at a high frequency. One resistant variant, 12662R, was further...... characterized and shown to be an adsorption mutant. Plaque assays using our large phage collection showed that seven out of 36 diverse capsular polysaccharide (CPS)-dependent phages could not infect 12662R, whereas the remaining phages formed plaques on 12662R with reduced efficiencies. Analysis of the CPS...

  12. An alternative approach to exact wave functions for time-dependent coupled oscillator model of charged particle in variable magnetic field

    International Nuclear Information System (INIS)

    Menouar, Salah; Maamache, Mustapha; Choi, Jeong Ryeol

    2010-01-01

    The quantum states of time-dependent coupled oscillator model for charged particles subjected to variable magnetic field are investigated using the invariant operator methods. To do this, we have taken advantage of an alternative method, so-called unitary transformation approach, available in the framework of quantum mechanics, as well as a generalized canonical transformation method in the classical regime. The transformed quantum Hamiltonian is obtained using suitable unitary operators and is represented in terms of two independent harmonic oscillators which have the same frequencies as that of the classically transformed one. Starting from the wave functions in the transformed system, we have derived the full wave functions in the original system with the help of the unitary operators. One can easily take a complete description of how the charged particle behaves under the given Hamiltonian by taking advantage of these analytical wave functions.

  13. Origins of intersubject variability of blood oxygenation level dependent and arterial spin labeling fMRI: implications for quantification of brain activity.

    Science.gov (United States)

    Gaxiola-Valdez, Ismael; Goodyear, Bradley G

    2012-12-01

    Accurate localization of brain activity using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been challenged because of the large BOLD signal within distal veins. Arterial spin labeling (ASL) techniques offer greater sensitivity to the microvasculature but possess low temporal resolution and limited brain coverage. In this study, we show that the physiological origins of BOLD and ASL depend on whether percent change or statistical significance is being considered. For BOLD and ASL fMRI data collected during a simple unilateral hand movement task, we found that in the area of the contralateral motor cortex the centre of gravity (CoG) of the intersubject coefficient of variation (CV) of BOLD fMRI was near the brain surface for percent change in signal, whereas the CoG of the intersubject CV for Z-score was in close proximity of sites of brain activity for both BOLD and ASL. These findings suggest that intersubject variability of BOLD percent change is vascular in origin, whereas the origin of inter-subject variability of Z-score is neuronal for both BOLD and ASL. For longer duration tasks (12 s or greater), however, there was a significant correlation between BOLD and ASL percent change, which was not evident for short duration tasks (6 s). These findings suggest that analyses directly comparing percent change in BOLD signal between pre-defined regions of interest using short duration stimuli, as for example in event-related designs, may be heavily weighted by large-vessel responses rather than neuronal responses. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Sensitivity of Photosynthetic Gas Exchange and Growth of Lodgepole Pine to Climate Variability Depends on the Age of Pleistocene Glacial Surfaces

    Science.gov (United States)

    Osborn, B.; Chapple, W.; Ewers, B. E.; Williams, D. G.

    2014-12-01

    The interaction between soil conditions and climate variability plays a central role in the ecohydrological functions of montane conifer forests. Although soil moisture availability to trees is largely dependent on climate, the depth and texture of soil exerts a key secondary influence. Multiple Pleistocene glacial events have shaped the landscape of the central Rocky Mountains creating a patchwork of soils differing in age and textural classification. This mosaic of soil conditions impacts hydrological properties, and montane conifer forests potentially respond to climate variability quite differently depending on the age of glacial till and soil development. We hypothesized that the age of glacial till and associated soil textural changes exert strong control on growth and photosynthetic gas exchange of lodgepole pine. We examined physiological and growth responses of lodgepole pine to interannual variation in maximum annual snow water equivalence (SWEmax) of montane snowpack and growing season air temperature (Tair) and vapor pressure deficit (VPD) across a chronosequence of Pleistocene glacial tills ranging in age from 700k to 12k years. Soil textural differences across the glacial tills illustrate the varying degrees of weathering with the most well developed soils with highest clay content on the oldest till surfaces. We show that sensitivity of growth and carbon isotope discrimination, an integrated measure of canopy gas exchange properties, to interannual variation SWEmax , Tair and VPD is greatest on young till surfaces, whereas trees on old glacial tills with well-developed soils are mostly insensitive to these interannual climate fluctuations. Tree-ring widths were most sensitive to changes in SWEmax on young glacial tills (p < 0.01), and less sensitive on the oldest till (p < 0.05). Tair correlates strongly with δ13C values on the oldest and youngest tills sites, but shows no significant relationship on the middle aged glacial till. It is clear that

  15. Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

    Science.gov (United States)

    Bredewold, Remco; Smith, Caroline J. W.; Dumais, Kelly M.; Veenema, Alexa H.

    2014-01-01

    We recently demonstrated that vasopressin (AVP) in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments) affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT) modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage) as opposed to familiar (home cage) social environments. Administration of the specific AVP V1a receptor (V1aR) antagonist (CH2)5Tyr(Me2)AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH2)5−[Tyr(Me)2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior. PMID:24982623

  16. Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

    Directory of Open Access Journals (Sweden)

    Remco eBredewold

    2014-06-01

    Full Text Available We recently demonstrated that vasopressin (AVP in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage as opposed to familiar (home cage social environments. Administration of the specific AVP V1a receptor (V1aR antagonist (CH25Tyr(Me2AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH25-[Tyr(Me2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze, but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.

  17. Intra- and inter-individual variability of Aspergillus fumigatus reactive T-cell frequencies in healthy volunteers in dependency of mould exposure in residential and working environment.

    Science.gov (United States)

    Wurster, Sebastian; Weis, Philipp; Page, Lukas; Helm, Johanna; Lazariotou, Maria; Einsele, Hermann; Ullmann, Andrew J

    2017-10-01

    Invasive aspergillosis remains a deadly disease in immunocompromised patients, whereas the combination of an exaggerated immune response and continuous exposure lead to various hyperinflammatory diseases. This pilot study aimed to gain an overview of the intra- and inter-individual variability in Aspergillus fumigatus reactive T-helper cells in healthy adults and the correlation with environmental mould exposure. In this flow cytometric study, the frequencies of CD154 + A. fumigatus reactive T cells were evaluated in 70 healthy volunteers. All subjects completed a standardised questionnaire addressing their mould exposure. Subjects with intensive mould exposure in their professional or residential surrounding demonstrated considerably higher mean frequencies of A. fumigatus reactive T-helper and T-memory cells. Comparative evaluation of multiple measurements over time demonstrated relatively conserved reactive T-cell frequencies in the absence of major changes to the exposure profile, whereas those frequently exposed in professional environment or with changes to their risk score demonstrated a marked dependency of antigen reactive T-cell frequencies on recent mould exposure. This pilot study was the first to provide data on the intra-individual variability in A. fumigatus reactive T-cell frequencies and its linkage to mould encounter. Fungus reactive T cells are to be considered a valued tool for the assessment of environmental mould exposure. © 2017 Blackwell Verlag GmbH.

  18. Self-produced Time Intervals Are Perceived as More Variable and/or Shorter Depending on Temporal Context in Subsecond and Suprasecond Ranges

    Directory of Open Access Journals (Sweden)

    Keita eMitani

    2016-06-01

    Full Text Available The processing of time intervals is fundamental for sensorimotor and cognitive functions. Perceptual and motor timing are often performed concurrently (e.g., playing a musical instrument. Although previous studies have shown the influence of body movements on time perception, how we perceive self-produced time intervals has remained unclear. Furthermore, it has been suggested that the timing mechanisms are distinct for the sub- and suprasecond ranges. Here, we compared perceptual performances for self-produced and passively presented time intervals in random contexts (i.e., multiple target intervals presented in a session across the sub- and suprasecond ranges (Experiment 1 and within the sub- (Experiment 2 and suprasecond (Experiment 3 ranges, and in a constant context (i.e., a single target interval presented in a session in the sub- and suprasecond ranges (Experiment 4. We show that self-produced time intervals were perceived as shorter and more variable across the sub- and suprasecond ranges and within the suprasecond range but not within the subsecond range in a random context. In a constant context, the self-produced time intervals were perceived as more variable in the suprasecond range but not in the subsecond range. The impairing effects indicate that motor timing interferes with perceptual timing. The dependence of impairment on temporal contexts suggests multiple timing mechanisms for the subsecond and suprasecond ranges. In addition, violation of the scalar property (i.e., a constant variability to target interval ratio was observed between the sub- and suprasecond ranges. The violation was clearer for motor timing than for perceptual timing. This suggests that the multiple timing mechanisms for the sub- and suprasecond ranges overlap more for perception than for motor. Moreover, the central tendency effect (i.e., where shorter base intervals are overestimated and longer base intervals are underestimated disappeared with subsecond

  19. Impact of supplier-specific investments in inter-organisational information systems on strategic electronic coordination: the moderation effect of buyer dependence

    Directory of Open Access Journals (Sweden)

    Teryokhin Sergei

    2018-03-01

    Full Text Available This paper examines the factors which influence sharing of the strategic information (in other words, electronic coordination in a buyer–supplier dyad. The antecedents of this coordination are examined rather well in the transaction cost economics (TCE theory and resource-dependency theory (RDT, while the supply chain management perspective is contemplated. The mentioned frameworks are used in the analysis. However, the research focus is narrowed down to the exploration of the antecedents of information exchange conducted via inter-organisational information systems (IOS. The empirical analysis is based on 198 observations of Norwegian companies operating in different types of industries. A regression model is used to test the hypotheses about the antecedents of strategic electronic coordination. The research results indicate that the direct effect of the supplier-specific investments in the IOS on the exchange of strategic information in the buyer–supplier dyad is not statistically significant. The supplier-specific investment in the IOS becomes positively associated with the strategic information exchange in the buyer–supplier dyad only when the buyer is dependent on the supplier. The buyer dependency creates a high motivation for the company to exchange the strategic information with the supplier who is more powerful in the dyad. This research concludes that the companies making substantial investments in the IOS for electronic coordination purposes may not reach their goals if relation-specific factors, such as buyer dependency, are not comprehensively considered.

  20. Stimulus Dependency of Object-Evoked Responses in Human Visual Cortex: An Inverse Problem for Category Specificity

    Science.gov (United States)

    Graewe, Britta; De Weerd, Peter; Farivar, Reza; Castelo-Branco, Miguel

    2012-01-01

    Many studies have linked the processing of different object categories to specific event-related potentials (ERPs) such as the face-specific N170. Despite reports showing that object-related ERPs are influenced by visual stimulus features, there is consensus that these components primarily reflect categorical aspects of the stimuli. Here, we re-investigated this idea by systematically measuring the effects of visual feature manipulations on ERP responses elicited by both structure-from-motion (SFM)-defined and luminance-defined object stimuli. SFM objects elicited a novel component at 200–250 ms (N250) over parietal and posterior temporal sites. We found, however, that the N250 amplitude was unaffected by restructuring SFM stimuli into meaningless objects based on identical visual cues. This suggests that this N250 peak was not uniquely linked to categorical aspects of the objects, but is strongly determined by visual stimulus features. We provide strong support for this hypothesis by parametrically manipulating the depth range of both SFM- and luminance-defined object stimuli and showing that the N250 evoked by SFM stimuli as well as the well-known N170 to static faces were sensitive to this manipulation. Importantly, this effect could not be attributed to compromised object categorization in low depth stimuli, confirming a strong impact of visual stimulus features on object-related ERP signals. As ERP components linked with visual categorical object perception are likely determined by multiple stimulus features, this creates an interesting inverse problem when deriving specific perceptual processes from variations in ERP components. PMID:22363479

  1. The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms.

    Science.gov (United States)

    Durocher, D; Taylor, I A; Sarbassova, D; Haire, L F; Westcott, S L; Jackson, S P; Smerdon, S J; Yaffe, M B

    2000-11-01

    Forkhead-associated (FHA) domains are a class of ubiquitous signaling modules that appear to function through interactions with phosphorylated target molecules. We have used oriented peptide library screening to determine the optimal phosphopeptide binding motifs recognized by several FHA domains, including those within a number of DNA damage checkpoint kinases, and determined the X-ray structure of Rad53p-FHA1, in complex with a phospho-threonine peptide, at 1.6 A resolution. The structure reveals a striking similarity to the MH2 domains of Smad tumor suppressor proteins and reveals a mode of peptide binding that differs from SH2, 14-3-3, or PTB domain complexes. These results have important implications for DNA damage signaling and CHK2-dependent tumor suppression, and they indicate that FHA domains play important and unsuspected roles in S/T kinase signaling mechanisms in prokaryotes and eukaryotes.

  2. Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation

    OpenAIRE

    Dorado, Beatriz; Area, Estela; Akman, Hasan O.; Hirano, Michio

    2010-01-01

    Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion. To determine the bases of disease onset, organ specificity and severity of TK2 deficiency, we have carefully characterized Tk2 H126N knockin mice (Tk2−/−). Although normal until postnatal day 8, Tk2−/− mice rapidly develop fatal encephalomyopathy between postnatal days 10 and 13. We have observed that wild-type Tk2 activity is constant in t...

  3. Magnetic field dependence of the specific heat of heavy-fermion YbCu4.5

    International Nuclear Information System (INIS)

    Amato, A.; Fisher, R.A.; Phillips, N.E.; Jaccard, D.; Walker, E.

    1990-03-01

    The specific heat of a polycrystalline sample of YbCu 4.5 has been measured between 0.3 and 20K in magnetic fields to 7T. At zero field a minimum in C/T is observed near 11K. Below that temperature C/T increases and below 0.5K exhibits an upturn ascribed to a hyperfine contribution. The increase in C/T below 11K is reduced by a factor 1.5 for H = 7T, whereas the hyperfine term is enhanced due to the contribution of the 63 Cu and 65 Cu and nuclei. 5 refs., 3 figs

  4. The NKG2D ligand ULBP2 is specifically regulated through an invariant chain-dependent endosomal pathway

    DEFF Research Database (Denmark)

    Uhlenbrock, Franziska Katharina; Hagemann-Jensen, Michael Henrik; Kehlet, Stephanie

    2014-01-01

    by affecting endosomal/lysosomal integrity and protein kinase C activity. The invariant chain was further essential for endosomal transport of ULBP2. This novel pathway was identified through screening experiments by which methylselenic acid was found to possess notable NKG2D ligand regulatory properties....... The protein kinase C inhibitor methylselenic acid induced MICA/B surface expression but dominantly blocked ULBP2 surface transport. Remarkably, by targeting this novel pathway we could specifically block the production of soluble ULBP2 from different, primary melanomas. Our findings strongly suggest...

  5. Effect of short-term heart rate variability biofeedback on long-term abstinence in alcohol dependent patients - a one-year follow-up.

    Science.gov (United States)

    Penzlin, Ana Isabel; Barlinn, Kristian; Illigens, Ben Min-Woo; Weidner, Kerstin; Siepmann, Martin; Siepmann, Timo

    2017-09-06

    A randomized controlled study (RCT) recently showed that short-term heart rate variability (HRV) biofeedback in addition to standard rehabilitation care for alcohol dependence can reduce craving, anxiety and improve cardiovascular autonomic function. In this one-year follow-up study we aimed to explore whether completion of 2-week HRV-Biofeedback training is associated with long-term abstinence. Furthermore, we sought to identify potential predictors of post-treatment abstinence. We conducted a survey on abstinence in patients with alcohol dependence 1 year after completion of an RCT comparing HRV-biofeedback in addition to inpatient rehabilitation treatment alone (controls). Abstinence rates were compared and analysed for association with demographic data as well as psychometric and autonomic cardiac assessment before and after completion of the biofeedback training using bivariate and multivariate regression analyses. Out of 48 patients who participated in the RCT, 27 patients (9 females, ages 42.9 ± 8.6, mean ± SD) completed our one-year follow-up. When including in the analysis only patients who completed follow-up, the rate of abstinence tended to be higher in patients who underwent HRV-biofeedback 1 year earlier compared to those who received rehabilitative treatment alone (66.7% vs 50%, p = ns). This non-significant trend was also observed in the intention-to-treat analysis where patients who did not participate in the follow-up were assumed to have relapsed (46,7% biofeedback vs. 33.3% controls, p = ns). Neither cardiac autonomic function nor psychometric variables were associated with abstinence 1 year after HRV-biofeedback. Our follow-up study provide a first indication of possible increase in long-term abstinence after HRV-biofeedback for alcohol dependence in addition to rehabilitation. The original randomized controlled trial was registered in the German Clinical Trials Register ( DRKS00004618 ). This one-year follow-up survey has not been

  6. Reminiscence therapy using odor in alcohol-dependent patients--psychophysiological evaluation and psychological evaluation; power spectral analysis of heart rate variability.

    Science.gov (United States)

    Arizono, H; Morita, N; Iizuka, S; Satoh, S; Nakatani, Y

    2000-12-01

    This research was based on the hypothesis that when alcohol-dependent patients describe themselves, awakening of emotion by affirmative odor stimulation may facilitate memory reframing focusing on more affirmative emotion and memories. To prove the hypothesis, physiological changes accompanied by emotional awakening were evaluated by measuring the autonomic activity. In addition, subjective evaluation by a self-report manner was examined to investigate the effectiveness of Reminiscence Therapy (RT) using odor in alcohol-dependent patients. Thirty-four patients who met the DSM-IV criteria of alcohol-related disorders and were hospitalized in a ward specialized to alcohol dependence therapy. Each patient underwent a one-to-one interview twice. For counterbalance, one interview was performed with odor stimulation using an odor with a relaxing effect that recall pleasant emotion, and the other was without odor stimulation. As the evaluation indices of physiological changes accompanied by emotional awakening, index of autonomic function (HRV; Heart rate variability) for objective evaluation and psychological indices (STAI; State-Trait Anxiety Inventory VAS; Visual Analog Scale) for subjective evaluation were measured. 1) Objective evaluation: Regarding the evaluation index of the autonomic function, the sympathetic nervous system activity (LF/HF; low frequency component/high frequency component ratio) was significantly inhibited by odor stimulation (p Subjective evaluation: Compared to the state prior to interview, state anxiety judged by STAI was significantly decreased after interview (p subjective evaluation, but the objective evaluation suggested that the odor inhibited the sympathetic nervous system. Thus, it was suggested that odor can be used in RT, that is, emotional changes due to stimulation of odor may be applicable in RT.

  7. Threshold-dependent variability of coronary artery calcification measurements - implications for contrast-enhanced multi-detector row-computed tomography

    International Nuclear Information System (INIS)

    Moselewski, Fabian; Ferencik, Maros; Achenbach, Stephan; Abbara, Suhny; Cury, Ricardo C.; Booth, Sarah L.; Jang, Ik-Kyung; Brady, Thomas J.; Hoffmann, Udo

    2006-01-01

    Introduction: The present study investigated the threshold-dependent variability of coronary artery calcification (CAC) measurements and the potential to quantify CAC in contrast-enhanced multi-detector row-computed tomography (MDCT). Methods: We compared the mean CT attenuation of CAC to luminal contrast enhancement of the coronary arteries in 30 patients (n = 30) undergoing standard coronary contrast-enhanced spiral MDCT. The modified Agatston score [AS], calcified plaque volume [CV], and mineral mass [MM]) at four different thresholds (130, 200, 300, and 400 HU) were measured in 50 patients who underwent non-contrast-enhanced MDCT. Results: Mean CT attenuation of CAC was similar to the attenuation of the contrast-enhanced coronary lumen (CAC 297.1 ± 68.7 HU versus 295 ± 65 HU (p < 0.0001), respectively). Above a threshold of 300 HU CAC measurements significantly varied to standard measurements obtained at a threshold of 130 HU (p < 0.0001). The threshold-dependent variation of MM measurements was significantly smaller than for AS and CV (130 HU versus 400 HU: 63, 75, and 81, respectively; p < 0.001). These differences resulted in a change of age and gender based percentile category for AS in 78% of subjects. Discussion: We demonstrated that CAC measurements are threshold dependent with MM measurements having significantly less variation than AS or CV. Due to the similarity of mean CT attenuation of CAC and the contrast-enhanced coronary lumen accurate quantification of CAC may be difficult in standard coronary contrast-enhanced spiral MDCT

  8. Threshold-dependent variability of coronary artery calcification measurements - implications for contrast-enhanced multi-detector row-computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Moselewski, Fabian [Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Ferencik, Maros [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Achenbach, Stephan [Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Department of Internal Medicine II (Cardiology), University of Erlangen (Germany); Abbara, Suhny [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Cury, Ricardo C. [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Booth, Sarah L. [Jean Mayer USDA Human Nutrition Research Center on Aging, 711 Washington St., Boston, MA 02114 (United States); Jang, Ik-Kyung [Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Brady, Thomas J. [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Hoffmann, Udo [Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)]. E-mail: uhoffman@partners.org

    2006-03-15

    Introduction: The present study investigated the threshold-dependent variability of coronary artery calcification (CAC) measurements and the potential to quantify CAC in contrast-enhanced multi-detector row-computed tomography (MDCT). Methods: We compared the mean CT attenuation of CAC to luminal contrast enhancement of the coronary arteries in 30 patients (n = 30) undergoing standard coronary contrast-enhanced spiral MDCT. The modified Agatston score [AS], calcified plaque volume [CV], and mineral mass [MM] at four different thresholds (130, 200, 300, and 400 HU) were measured in 50 patients who underwent non-contrast-enhanced MDCT. Results: Mean CT attenuation of CAC was similar to the attenuation of the contrast-enhanced coronary lumen (CAC 297.1 {+-} 68.7 HU versus 295 {+-} 65 HU (p < 0.0001), respectively). Above a threshold of 300 HU CAC measurements significantly varied to standard measurements obtained at a threshold of 130 HU (p < 0.0001). The threshold-dependent variation of MM measurements was significantly smaller than for AS and CV (130 HU versus 400 HU: 63, 75, and 81, respectively; p < 0.001). These differences resulted in a change of age and gender based percentile category for AS in 78% of subjects. Discussion: We demonstrated that CAC measurements are threshold dependent with MM measurements having significantly less variation than AS or CV. Due to the similarity of mean CT attenuation of CAC and the contrast-enhanced coronary lumen accurate quantification of CAC may be difficult in standard coronary contrast-enhanced spiral MDCT.

  9. Density dependence and climate effects in Rocky Mountain elk: an application of regression with instrumental variables for population time series with sampling error.

    Science.gov (United States)

    Creel, Scott; Creel, Michael

    2009-11-01

    1. Sampling error in annual estimates of population size creates two widely recognized problems for the analysis of population growth. First, if sampling error is mistakenly treated as process error, one obtains inflated estimates of the variation in true population trajectories (Staples, Taper & Dennis 2004). Second, treating sampling error as process error is thought to overestimate the importance of density dependence in population growth (Viljugrein et al. 2005; Dennis et al. 2006). 2. In ecology, state-space models are used to account for sampling error when estimating the effects of density and other variables on population growth (Staples et al. 2004; Dennis et al. 2006). In econometrics, regression with instrumental variables is a well-established method that addresses the problem of correlation between regressors and the error term, but requires fewer assumptions than state-space models (Davidson & MacKinnon 1993; Cameron & Trivedi 2005). 3. We used instrumental variables to account for sampling error and fit a generalized linear model to 472 annual observations of population size for 35 Elk Management Units in Montana, from 1928 to 2004. We compared this model with state-space models fit with the likelihood function of Dennis et al. (2006). We discuss the general advantages and disadvantages of each method. Briefly, regression with instrumental variables is valid with fewer distributional assumptions, but state-space models are more efficient when their distributional assumptions are met. 4. Both methods found that population growth was negatively related to population density and winter snow accumulation. Summer rainfall and wolf (Canis lupus) presence had much weaker effects on elk (Cervus elaphus) dynamics [though limitation by wolves is strong in some elk populations with well-established wolf populations (Creel et al. 2007; Creel & Christianson 2008)]. 5. Coupled with predictions for Montana from global and regional climate models, our results

  10. Extensive gene-specific translational reprogramming in a model of B cell differentiation and Abl-dependent transformation.

    Directory of Open Access Journals (Sweden)

    Jamie G Bates

    Full Text Available To what extent might the regulation of translation contribute to differentiation programs, or to the molecular pathogenesis of cancer? Pre-B cells transformed with the viral oncogene v-Abl are suspended in an immortalized, cycling state that mimics leukemias with a BCR-ABL1 translocation, such as Chronic Myelogenous Leukemia (CML and Acute Lymphoblastic Leukemia (ALL. Inhibition of the oncogenic Abl kinase with imatinib reverses transformation, allowing progression to the next stage of B cell development. We employed a genome-wide polysome profiling assay called Gradient Encoding to investigate the extent and potential contribution of translational regulation to transformation and differentiation in v-Abl-transformed pre-B cells. Over half of the significantly translationally regulated genes did not change significantly at the level of mRNA abundance, revealing biology that might have been missed by measuring changes in transcript abundance alone. We found extensive, gene-specific changes in translation affecting genes with known roles in B cell signaling and differentiation, cancerous transformation, and cytoskeletal reorganization potentially affecting adhesion. These results highlight a major role for gene-specific translational regulation in remodeling the gene expression program in differentiation and malignant transformation.

  11. Effect of silver nanoparticles on Mediterranean sea urchin embryonal development is species specific and depends on moment of first exposure.

    Science.gov (United States)

    Burić, Petra; Jakšić, Željko; Štajner, Lara; Dutour Sikirić, Maja; Jurašin, Darija; Cascio, Claudia; Calzolai, Luigi; Lyons, Daniel Mark

    2015-10-01

    With the ever growing use of nanoparticles in a broad range of industrial and consumer applications there is increasing likelihood that such nanoparticles will enter the aquatic environment and be transported through freshwater systems, eventually reaching estuarine or marine waters. Due to silver's known antimicrobial properties and widespread use of silver nanoparticles (AgNP), their environmental fate and impact is therefore of particular concern. In this context we have investigated the species-specific effects of low concentrations of 60 nm AgNP on embryonal development in Mediterranean sea urchins Arbacia lixula, Paracentrotus lividus and Sphaerechinus granularis. The sensitivity of urchin embryos was tested by exposing embryos to nanoparticle concentrations in the 1-100 μg L(-1) range, with times of exposure varying from 30 min to 24 h (1 h-48 h for S. granularis) post-fertilisation which corresponded with fertilized egg, 4 cell, blastula and gastrula development phases. The most sensitive species to AgNP was A. lixula with significant modulation of embryonal development at the lowest AgNP concentrations of 1-10 μg L(-1) with high numbers of malformed embryos or arrested development. The greatest impact on development was noted for those embryos first exposed to nanoparticles at 6 and 24 h post fertilisation. For P. lividus, similar effects were noted at higher concentrations of 50 μg L(-1) and 100 μg L(-1) for all times of first exposure. The S. granularis embryos indicated a moderate AgNP impact, and significant developmental abnormalities were recorded in the concentration range of 10-50 μg L(-1). As later post-fertilisation exposure times to AgNP caused greater developmental changes in spite of a shorter total exposure time led us to postulate on additional mechanisms of AgNP toxicity. The results herein indicate that toxic effects of AgNP are species-specific. The moment at which embryos first encounter AgNP is also shown to be

  12. Effect of partial and complete variable loop deletions of the human immunodeficiency virus type 1 envelope glycoprotein on the breadth of gp160-specific immune responses

    International Nuclear Information System (INIS)

    Gzyl, Jaroslaw; Bolesta, Elizabeth; Wierzbicki, Andrew; Kmieciak, Dariusz; Naito, Toshio; Honda, Mitsuo; Komuro, Katsutoshi; Kaneko, Yutaro; Kozbor, Danuta

    2004-01-01

    Induction of cross-reactive cellular and humoral responses to the HIV-1 envelope (env) glycoprotein was examined after DNA immunization of BALB/c mice with gp140 89.6 -derived constructs exhibiting partial or complete deletions of the V1, V2, and V3 domains. It was demonstrated that specific modification of the V3 loop (mV3) in combination with the V2-modified (mV2) or V1/V2-deleted (ΔV1/V2) region elicited increased levels of cross-reactive CD8 + T cell responses. Mice immunized with the mV2/mV3 or ΔV1/V2/mV3 gp140 89.6 plasmid DNA were greater than 50-fold more resistant to challenge with recombinant vaccinia virus (rVV) expressing heterologous env gene products than animals immunized with the wild-type (WT) counterpart. Sera from mV2/mV3- and ΔV1/V2/mV3-immunized mice exhibited the highest cross-neutralizing activity and displayed intermediate antibody avidity values which were further enhanced by challenge with rVV expressing the homologous gp160 glycoprotein. In contrast, complete deletion of the variable regions had little or no effect on the cross-reactive antibody responses. The results of these experiments indicate that the breadth of antibody responses to the HIV-1 env glycoprotein may not be increased by removal of the variable domains. Instead, partial deletions within these regions may redirect specific responses toward conserved epitopes and facilitate approaches for boosting cross-reactive cellular and antibody responses to the env glycoprotein

  13. Elimination of Endogenous Toxin, Creatinine from Blood Plasma Depends on Albumin Conformation: Site Specific Uremic Toxicity & Impaired Drug Binding

    Science.gov (United States)

    Varshney, Ankita; Rehan, Mohd; Subbarao, Naidu; Rabbani, Gulam; Khan, Rizwan Hasan

    2011-01-01

    Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state. PMID:21386972

  14. In vitro cell quality of articular chondrocytes assigned for autologous implantation in dependence of specific patient characteristics

    DEFF Research Database (Denmark)

    Pestka, Jan M; Schmal, Hagen; Salzmann, Gian

    2011-01-01

    OBJECTIVE: Autologous chondrocyte implantation (ACI) is a well-established therapeutic option for the treatment of cartilage defects of the knee joint. Since information concerning the cellular aspects of ACI is still limited, the aim of the present study was to investigate relevant differences...... between chondrocyte quality after in vitro cultivation and possible correlations with patient-specific factors. DESIGN: Cell quality of 252 consecutive ACI patients was assessed after chondrocyte in vitro expansion by determination of the expression of cartilage relevant surface marker CD44 and cartilage......, aggrecan or collagen type II nor cell density or viability after proliferation seemed to correlate with the grade of joint degeneration, defect aetiology or patient gender. However, chondrocytes harvested from the knee joints of patients at less than 20 years of age showed significantly higher expression...

  15. Expression, purification, crystallization and preliminary X-ray analysis of NAD(P)H-dependent carbonyl reductase specifically expressed in thyroidectomized chicken fatty liver

    International Nuclear Information System (INIS)

    Yoneda, Kazunari; Fukuda, Yudai; Shibata, Takeshi; Araki, Tomohiro; Nikki, Takahiro; Sakuraba, Haruhiko; Ohshima, Toshihisa

    2012-01-01

    An NAD(P)H-dependent carbonyl reductase specifically expressed in thyroidectomized chicken fatty liver was successfully isolated and crystallized. An NAD(P)H-dependent carbonyl reductase specifically expressed in thyroidectomized chicken fatty liver was crystallized using the sitting-drop vapour-diffusion method with polyethylene glycol 300 as the precipitant. The crystals belonged to the monoclinic space group C2, with unit-cell parameters a = 104.26, b = 81.32, c = 77.27 Å, β = 119.43°, and diffracted to 1.86 Å resolution on beamline NE3A at the Photon Factory. The overall R merge was 5.4% and the data completeness was 99.4%

  16. Generic and sequence-variant specific molecular assays for the detection of the highly variable Grapevine leafroll-associated virus 3.

    Science.gov (United States)

    Chooi, Kar Mun; Cohen, Daniel; Pearson, Michael N

    2013-04-01

    Grapevine leafroll-associated virus 3 (GLRaV-3) is an economically important virus, which is found in all grapevine growing regions worldwide. Its accurate detection in nursery and field samples is of high importance for certification schemes and disease management programmes. To reduce false negatives that can be caused by sequence variability, a new universal primer pair was designed against a divergent sequence data set, targeting the open reading frame 4 (heat shock protein 70 homologue gene), and optimised for conventional one-step RT-PCR and one-step SYBR Green real-time RT-PCR assays. In addition, primer pairs for the simultaneous detection of specific GLRaV-3 variants from groups 1, 2, 6 (specifically NZ-1) and the outlier NZ2 variant, and the generic detection of variants from groups 1 to 5 were designed and optimised as a conventional one-step multiplex RT-PCR assay using the plant nad5 gene as an internal control (i.e. one-step hexaplex RT-PCR). Results showed that the generic and variant specific assays detected in vitro RNA transcripts from a range of 1×10(1)-1×10(8) copies of amplicon per μl diluted in healthy total RNA from Vitis vinifera cv. Cabernet Sauvignon. Furthermore, the assays were employed effectively to screen 157 germplasm and 159 commercial field samples. Thus results demonstrate that the GLRaV-3 generic and variant-specific assays are prospective tools that will be beneficial for certification schemes and disease management programmes, as well as biological and epidemiological studies of the divergent GLRaV-3 populations. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-23

    p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In this study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis. - Highlights: • PF-4708671, a S6K1-specific inhibitor, prevents S6K1-mediated S6 phosphorylation. • However, PF-4708671 treatment often leads to apoptotic cell death. • Protective mechanism against PF-4708671-induced cell death remains to be elucidated. • PF-4708671 induced p62-dependent, autophagic Keap1 degradation-mediated Nrf2 activation. • p62-dependent Nrf2 activation protects cells from PF-4708671-mediated apoptosis.

  18. An Examination by Site-Directed Mutagenesis of Putative Key Residues in the Determination of Coenzyme Specificity in Clostridial NAD+-Dependent Glutamate Dehydrogenase

    Directory of Open Access Journals (Sweden)

    Joanna Griffin

    2011-01-01

    Full Text Available Sequence and structure comparisons of various glutamate dehydrogenases (GDH and other nicotinamide nucleotide-dependent dehydrogenases have potentially implicated certain residues in coenzyme binding and discrimination. We have mutated key residues in Clostridium symbiosum NAD+-specific GDH to investigate their contribution to specificity and to enhance acceptance of NADPH. Comparisons with E. coli NADPH-dependent GDH prompted design of mutants F238S, P262S, and F238S/P262S, which were purified and assessed at pH 6.0, 7.0, and 8.0. They showed markedly increased catalytic efficiency with NADPH, especially at pH 8.0 (∼170-fold for P262S and F238S/P262S with relatively small changes for NADH. A positive charge introduced through the D263K mutation also greatly increased catalytic efficiency with NADPH (over 100-fold at pH 8 and slightly decreased activity with NADH. At position 242, “P6” of the “core fingerprint,” where NAD+- and NADP+-dependent enzymes normally have Gly or Ala, respectively, clostridial GDH already has Ala. Replacement with Gly produced negligible shift in coenzyme specificity.

  19. On vitamin D-dependent regulation of local mechanisms of non-specific defense in children with connective tissue dysplasia

    Directory of Open Access Journals (Sweden)

    L.I. Omelchenko

    2017-11-01

    Full Text Available Background. The influence of active vitamin D (VD metabolites on the reaction of nonspecific defense mechanisms of mucous membranes may be of particular importance in children with connective tissue dysplasia (СТD. The purpose of the study was to establish the concentration of human -defensin (HBD-2 and lysozyme in local secretions in children with CTD taking into account the body’s VD supply. Materials and methods. We examined 127 children aged 11–17 years with phenotypic manifestations of CTD taking into account the supplementation of VD. Four groups of children were identified: group 1 — healthy children with a physiological level of 25OHD, group 2 — children with moderate and severe CTD degrees and physiological concentrations of VD (75–100 nmol/l, group 3 — children with CTD and 25OHD insufficiency (50–75 nmol/l, group 4 — children with CTD and vitamin D deficiency (VDD (below 50 nmol/l. Determination of HBD-2 level by immunoassay and lysozyme using a dry powder of one-day Micrococcus lyzodeiticus culture in local secretions (saliva, coprofiltrate (CF was performed in all children. Results. When studying HBD-2 in saliva, its highest concentrations were found in children of group 1 — 4.52 ± 0.06 ng/ml. Lower levels of HBD-2 were reported in children of groups 2 and 3, and in children with CTD and DVD, the rates were lowest — 3.88 ± 0.08 ng/ml. The highest HBD-2 concentrations in CF were detected in group 1 — 81.14 ± 5.13 ng/ml. In groups of children with dysplastic manifestations, a significant difference in data (p ≤ 0.05 is observed depending on the concentration of 25OHD, with the lowest concentrations found in VDD group — 52.63 ± 3.01 ng/ml. The highest lysozyme levels in CF were in children from groups 1 (4.68 ± 0.10 mg/l and 2 (4.41 ± 0.09 mg/l; however, the lowest concentration of lysozyme was found in children with CTD and VDD — 4.09 ± 0.08 mg/l. A direct relationship is determined between the

  20. Cyclin-dependent kinase 9 is a novel specific molecular target in adult T-cell leukemia/lymphoma.

    Science.gov (United States)

    Narita, Tomoko; Ishida, Takashi; Ito, Asahi; Masaki, Ayako; Kinoshita, Shiori; Suzuki, Susumu; Takino, Hisashi; Yoshida, Takashi; Ri, Masaki; Kusumoto, Shigeru; Komatsu, Hirokazu; Imada, Kazunori; Tanaka, Yuetsu; Takaori-Kondo, Akifumi; Inagaki, Hiroshi; Scholz, Arne; Lienau, Philip; Kuroda, Taruho; Ueda, Ryuzo; Iida, Shinsuke

    2017-08-31

    Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (RNAPII). The deregulation of CDK9/P-TEFb has important implications for many cancer types. BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase 1 studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL). As a result of CDK9 inhibition and subsequent inhibition of phosphorylation at serine 2 of the RNAPII CTD, BAY 1143572 decreased c-Myc and Mcl-1 levels in ATL-derived or human T-cell lymphotropic virus type-1 (HTLV-1)-transformed lines and primary ATL cells tested, leading to their growth inhibition and apoptosis. Median inhibitory concentrations for BAY 1143572 in ATL-derived or HTLV-1-transformed lines (n = 8), primary ATL cells (n = 11), and CD4 + cells from healthy volunteers (n = 5) were 0.535, 0.30, and 0.36 μM, respectively. Next, NOG mice were used as recipients of tumor cells from an ATL patient. BAY 1143572-treated ATL-bearing mice (once daily 12.5 mg/kg oral application) demonstrated significantly decreased ATL cell infiltration of the liver and bone marrow, as well as decreased human soluble interleukin-2 receptor levels in serum (reflecting the ATL tumor burden), compared with untreated mice (n = 8 for both). BAY 1143572-treated ATL-bearing mice demonstrated significantly prolonged survival compared with untreated ATL-bearing mice (n = 7 for both). Collectively, this study indicates that BAY 1143572 showed strong potential as a novel treatment of ATL. © 2017 by The American Society of Hematology.

  1. pH Dependence of a Mammalian Polyamine Oxidase: Insights into Substrate Specificity and the Role of Lysine 315†

    Science.gov (United States)

    Pozzi, Michelle Henderson; Gawandi, Vijay; Fitzpatrick, Paul F.

    2009-01-01

    Mammalian polyamine oxidases (PAO) catalyze the oxidation of N1-acetylspermine and N1-acetylspermidine to produce N-acetyl-3-aminopropanaldehyde and spermidine or putrescine. Structurally, PAO is a member of the monoamine oxidase family of flavoproteins. The effects of pH on kinetic parameters of mouse PAO have been determined to provide insight into the protonation state of the polyamine required for catalysis and the roles of ionizable residues in the active site in amine oxidation. For N1-acetylspermine, N1-acetylspermidine, and spermine, the kcat/Kamine-pH profiles are bell-shaped. In each case the profile agrees with that expected if the productive form of the substrate has a single positively charged nitrogen. The pKi-pH profiles for a series of polyamine analogs are most consistent with the nitrogen at the site of oxidation being neutral and one other nitrogen being positively charged in the reactive form of the substrate. With N1-acetylspermine as substrate, the value of kred, the limiting rate constant for flavin reduction, is pH dependent, decreasing below a pKa value of 7.3, again consistent with the requirement for an uncharged nitrogen for substrate oxidation. Lys315 in PAO corresponds to a conserved active site residue found throughout the monoamine oxidase family. Mutation of Lys315 to methionine has no effect on the kcat/Kamine profile for spermine, the kred value with N1-acetylspermine is only 1.8-fold lower in the mutant protein, and the pKa in the kred-pH profile with N1-acetylspermine shifts to 7.8. These results rule out Lys315 as a source of a pKa in the kcat/Kamine or kcat/kred profiles. They also establish that this residue does not play a critical role in amine oxidation by PAO. PMID:19199575

  2. DNA interactions with a Methylene Blue redox indicator depend on the DNA length and are sequence specific.

    Science.gov (United States)

    Farjami, Elaheh; Clima, Lilia; Gothelf, Kurt V; Ferapontova, Elena E

    2010-06-01

    A DNA molecular beacon approach was used for the analysis of interactions between DNA and Methylene Blue (MB) as a redox indicator of a hybridization event. DNA hairpin structures of different length and guanine (G) content were immobilized onto gold electrodes in their folded states through the alkanethiol linker at the 5'-end. Binding of MB to the folded hairpin DNA was electrochemically studied and compared with binding to the duplex structure formed by hybridization of the hairpin DNA to a complementary DNA strand. Variation of the electrochemical signal from the DNA-MB complex was shown to depend primarily on the DNA length and sequence used: the G-C base pairs were the preferential sites of MB binding in the duplex. For short 20 nts long DNA sequences, the increased electrochemical response from MB bound to the duplex structure was consistent with the increased amount of bound and electrochemically readable MB molecules (i.e. MB molecules that are available for the electron transfer (ET) reaction with the electrode). With longer DNA sequences, the balance between the amounts of the electrochemically readable MB molecules bound to the hairpin DNA and to the hybrid was opposite: a part of the MB molecules bound to the long-sequence DNA duplex seem to be electrochemically mute due to long ET distance. The increasing electrochemical response from MB bound to the short-length DNA hybrid contrasts with the decreasing signal from MB bound to the long-length DNA hybrid and allows an "off"-"on" genosensor development.

  3. On the Size Dependence of Molar and Specific Properties of Independent Nano-phases and Those in Contact with Other Phases

    Science.gov (United States)

    Kaptay, George

    2018-05-01

    Nano-materials are materials with at least one nano-phase. A nano-phase is a phase with at least one of its dimensions below 100 nm. It is shown here that nano-phases have at least 1% of their atoms along their surface layer. The ratio of surface atoms is proportional to the specific surface area of the phase, defined as the ratio of its surface area to its volume. Each specific/molar property has its bulk value and its surface value for the given phase, being always different, as the energetic states of the atoms in the bulk and in the surface layer of a phase are different. The average specific/molar property of a nano-phase is modeled here as a linear combination of the bulk and surface values of the same property, scaled with the ratio of the surface atoms. That makes the performance of all nano-phases proportional to their specific surface area. As the characteristic size of the nano-phase is inversely proportional to its specific surface area, all specific/molar properties of nano-phases are inversely proportional to the characteristic size of the phase. This is applied to the size dependence of the molar Gibbs energy of the nano-phase, which appears to be in agreement with the thermodynamics of Gibbs. This agreement proves the general validity of the present model on the size dependence of the specific/molar properties of independent nano-phases. It is shown that the properties of nano-phases are different for independent nano-phases (surrounded only by their equilibrium vapor phase) and for nano-phases in multi-phase situations, such as a liquid nano-droplet in the sessile drop configuration.

  4. Ion mobility studies of carbohydrates as group I adducts: isomer specific collisional cross section dependence on metal ion radius.

    Science.gov (United States)

    Huang, Yuting; Dodds, Eric D

    2013-10-15

    Carbohydrates play numerous critical roles in biological systems. Characterization of oligosaccharide structures is essential to a complete understanding of their functions in biological processes; nevertheless, their structural determination remains challenging in part due to isomerism. Ion mobility spectrometry provides the means to resolve gas phase ions on the basis of their shape-to-charge ratios, thus providing significant potential for separation and differentiation of carbohydrate isomers. Here, we report on the determination of collisional cross sections for four groups of isomeric carbohydrates (including five isomeric disaccharides, four isomeric trisaccharides, two isomeric pentasaccharides, and two isomeric hexasaccharides) as their group I metal ion adducts (i.e., [M + Li](+), [M + Na](+), [M + K](+), [M + Rb](+), and [M + Cs](+)). In all, 65 collisional cross sections were measured, the great majority of which have not been previously reported. As anticipated, the collisional cross sections of the carbohydrate metal ion adducts generally increase with increasing metal ion radius; however, the collisional cross sections were found to scale with the group I cation size in isomer specific manners. Such measurements are of substantial analytical value, as they illustrate how the selection of charge carrier influences carbohydrate ion mobility determinations. For example, certain pairs of isomeric carbohydrates assume unique collisional cross sections upon binding one metal ion, but not another. On the whole, these data suggest a role for the charge carrier as a probe of carbohydrate structure and thus have significant implications for the continued development and application of ion mobility spectrometry for the distinction and resolution of isomeric carbohydrates.

  5. Statistical mechanics of Roskilde liquids: configurational adiabats, specific heat contours, and density dependence of the scaling exponent.

    Science.gov (United States)

    Bailey, Nicholas P; Bøhling, Lasse; Veldhorst, Arno A; Schrøder, Thomas B; Dyre, Jeppe C

    2013-11-14

    We derive exact results for the rate of change of thermodynamic quantities, in particular, the configurational specific heat at constant volume, CV, along configurational adiabats (curves of constant excess entropy Sex). Such curves are designated isomorphs for so-called Roskilde liquids, in view of the invariance of various structural and dynamical quantities along them. The slope of the isomorphs in a double logarithmic representation of the density-temperature phase diagram, γ, can be interpreted as one third of an effective inverse power-law potential exponent. We show that in liquids where γ increases (decreases) with density, the contours of CV have smaller (larger) slope than configurational adiabats. We clarify also the connection between γ and the pair potential. A fluctuation formula for the slope of the CV-contours is derived. The theoretical results are supported with data from computer simulations of two systems, the Lennard-Jones fluid, and the Girifalco fluid. The sign of dγ∕dρ is thus a third key parameter in characterizing Roskilde liquids, after γ and the virial-potential energy correlation coefficient R. To go beyond isomorph theory we compare invariance of a dynamical quantity, the self-diffusion coefficient, along adiabats and CV-contours, finding it more invariant along adiabats.

  6. Degree of multicollinearity and variables involved in linear dependence in additive-dominant models Grau de multicolinearidade e variáveis envolvidas na dependência linear em modelos aditivo-dominantes

    Directory of Open Access Journals (Sweden)

    Juliana Petrini

    2012-12-01

    Full Text Available The objective of this work was to assess the degree of multicollinearity and to identify the variables involved in linear dependence relations in additive-dominant models. Data of birth weight (n=141,567, yearling weight (n=58,124, and scrotal circumference (n=20,371 of Montana Tropical composite cattle were used. Diagnosis of multicollinearity was based on the variance inflation factor (VIF and on the evaluation of the condition indexes and eigenvalues from the correlation matrix among explanatory variables. The first model studied (RM included the fixed effect of dam age class at calving and the covariates associated to the direct and maternal additive and non-additive effects. The second model (R included all the effects of the RM model except the maternal additive effects. Multicollinearity was detected in both models for all traits considered, with VIF values of 1.03 - 70.20 for RM and 1.03 - 60.70 for R. Collinearity increased with the increase of variables in the model and the decrease in the number of observations, and it was classified as weak, with condition index values between 10.00 and 26.77. In general, the variables associated with additive and non-additive effects were involved in multicollinearity, partially due to the natural connection between these covariables as fractions of the biological types in breed composition.O objetivo deste trabalho foi avaliar o grau de multicolinearidade e identificar as variáveis envolvidas na dependência linear em modelos aditivo-dominantes. Foram utilizados dados de peso ao nascimento (n=141.567, peso ao ano (n=58.124 e perímetro escrotal (n=20.371 de bovinos de corte compostos Montana Tropical. O diagnóstico de multicolinearidade foi baseado no fator de inflação de variância (VIF e no exame dos índices de condição e dos autovalores da matriz de correlações entre as variáveis explanatórias. O primeiro modelo estudado (RM incluiu o efeito fixo de classe de idade da mãe ao parto e

  7. Adolescent maturation of inhibitory inputs onto cingulate cortex neurons is cell-type specific and TrkB dependent

    Directory of Open Access Journals (Sweden)

    Angela eVandenberg

    2015-02-01

    Full Text Available The maturation of inhibitory circuits during adolescence may be tied to the onset of mental health disorders such as schizophrenia. Neurotrophin signaling likely plays a critical role in supporting inhibitory circuit development and is also implicated in psychiatric disease. Within the neocortex, subcircuits may mature at different times and show differential sensitivity to neurotrophin signaling. We measured miniature inhibitory and excitatory postsynaptic currents (mIPSC and mEPSCs in Layer 5 cell-types in the mouse anterior cingulate across the periadolescent period. We differentiated cell-types mainly by Thy1 YFP transgene expression and also retrobead injection labeling in the contralateral cingulate and ipsilateral pons. We found that YFP- neurons and commissural projecting neurons had lower frequency of mIPSCs than neighboring YFP+ neurons or pons projecting neurons in juvenile mice (P21-25. YFP- neurons and to a lesser extent commissural projecting neurons also showed a significant increase in mIPSC amplitude during the periadolescent period (P21-25 vs. P40-50, which was not seen in YFP+ neurons or pons projecting neurons. Systemic disruption of tyrosine kinase receptor B (TrkB signaling during P23-50 in TrkBF616A mice blocked developmental changes in mIPSC amplitude, without affecting miniature excitatory post synaptic currents (mEPSCs. Our data suggest that the maturation of inhibitory inputs onto layer 5 pyramidal neurons is cell-type specific. These data may inform our understanding of adolescent brain development across species and aid in identifying candidate subcircuits that may show greater vulnerability in mental illness.

  8. Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers

    Directory of Open Access Journals (Sweden)

    Rasool Suhail

    2007-09-01

    Full Text Available Abstract Background Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD, amyloid accumulates in several distinct types of insoluble plaque deposits, intracellular Aβ and as soluble oligomers and the relationships between these deposits and their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils. Results We immunized rabbits with a morphologically homogeneous population of Aβ42 fibrils. The resulting immune serum (OC specifically recognizes fibrils, but not random coil monomer or prefibrillar oligomers, indicating fibrils display a distinct conformation dependent epitope that is absent in prefibrillar oligomers. The fibril epitope is also displayed by fibrils of other types of amyloids, indicating that the epitope is a generic feature of the polypeptide backbone. The fibril specific antibody also recognizes 100,000 × G soluble fibrillar oligomers ranging in size from dimer to greater than 250 kDa on western blots. The fibrillar oligomers recognized by OC are immunologically distinct from prefibrillar oligomers recognized by A11, even though their sizes overlap broadly, indicating that size is not a reliable indicator of oligomer conformation. The immune response to prefibrillar oligomers and fibrils is not sequence specific and antisera of the same specificity are produced in response to immunization with islet amyloid polypeptide prefibrillar oligomer mimics and fibrils. The fibril specific antibodies stain all types of amyloid deposits in human AD brain. Diffuse amyloid deposits stain intensely with anti-fibril antibody although they are thioflavin S negative, suggesting that they are indeed fibrillar in conformation. OC also stains islet amyloid deposits in transgenic mouse models of type

  9. The adipokinetic hormone receptor modulates sexual behavior, pheromone perception and pheromone production in a sex-specific and starvation-dependent manner in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Sebastien eLebreton

    2016-01-01

    Full Text Available Food availability and nutritional status shape the reproductive activity of many animals. In rodents, hormones such as gonadotropin-releasing hormone (GnRH, restore energy homeostasis not only through regulating e.g. caloric intake and energy housekeeping, but also through modulating sex drive. We investigated whether the insect homologue of the GnRH receptor, the adipokinetic hormone receptor (AKHR modulates sexual behavior of the fruit fly Drosophila melanogaster depending on nutritional status. We found that AKHR regulates male, but not female sexual behavior in a starvation-dependent manner. Males lacking AKHR showed a severe decrease in their courtship activity when starved, as well as an increase in mating duration when fed. AKHR expression is particularly strong in the subesophageal zone (SEZ, Ito et al. 2014. We found axonal projections from AKHR-expressing neurons to higher brain centers including specific glomeruli in the antennal lobe. Among the glomeruli that received projections were those dedicated to detecting the male specific pheromone cis-vaccenyl acetate (cVA. Accordingly, responses to cVA were dependent on the nutritional status of flies. AKHR was also involved in the regulation of the production of cuticular pheromones, 7,11-heptacosadiene and 7-tricosene. This effect was observed only in females and depended on their feeding state. AKHR has therefore a dual role on both pheromone perception and production. For the first time our study shows an effect of AKHR on insect sexual behavior and physiology. Our results support the hypothesis of a conserved role of the GnRH/AKH pathway on a nutritional state-dependent regulation of reproduction in both vertebrates and invertebrates.

  10. Unit-specific calibration of Actigraph accelerometers in a mechanical setup - is it worth the effort? The effect on random output variation caused by technical inter-instrument variability in the laboratory and in the field

    DEFF Research Database (Denmark)

    Moeller, Niels C; Korsholm, Lars; Kristensen, Peter L

    2008-01-01

    BACKGROUND: Potentially, unit-specific in-vitro calibration of accelerometers could increase field data quality and study power. However, reduced inter-unit variability would only be important if random instrument variability contributes considerably to the total variation in field data. Therefor...

  11. Regulatory function of a novel population of mouse autoantigen-specific Foxp3 regulatory T cells depends on IFN-gamma, NO, and contact with target cells.

    Directory of Open Access Journals (Sweden)

    Cyndi Chen

    Full Text Available BACKGROUND: Both naturally arising Foxp3(+ and antigen-induced Foxp3(- regulatory T cells (Treg play a critical role in regulating immune responses, as well as in preventing autoimmune diseases and graft rejection. It is known that antigen-specific Treg are more potent than polyclonal Treg in suppressing pathogenic immune responses that cause autoimmunity and inflammation. However, difficulty in identifying and isolating a sufficient number of antigen-specific Treg has limited their use in research to elucidate the mechanisms underlying their regulatory function and their potential role in therapy. METHODOLOGY/PRINCIPAL FINDINGS: Using a novel class II MHC tetramer, we have isolated a population of CD4(+ Foxp3(- T cells specific for the autoantigen glutamic acid decarboxylase p286-300 peptide (NR286 T cells from diabetes-resistant non-obese resistant (NOR mice. These Foxp3(- NR286 T cells functioned as Treg that were able to suppress target T cell proliferation in vitro and inhibit type 1 diabetes in animals. Unexpected results from mechanistic studies in vitro showed that their regulatory function was dependent on not only IFN-gamma and nitric oxide, but also on cell contact with target cells. In addition, separating NR286 Treg from target T cells in transwell assays abolished both production of NO and suppression of target T cells, regardless of whether IFN-gamma was produced in cell cultures. Therefore, production of NO, not IFN-gamma, was cell contact dependent, suggesting that NO may function downstream of IFN-gamma in mediating regulatory function of NR286 Treg. CONCLUSIONS/SIGNIFICANCE: These studies identified a unique population of autoantigen-specific Foxp3(- Treg that can exert their regulatory function dependent on not only IFN-gamma and NO but also cell contact with target cells.

  12. Path Dependency

    OpenAIRE

    Mark Setterfield

    2015-01-01

    Path dependency is defined, and three different specific concepts of path dependency – cumulative causation, lock in, and hysteresis – are analyzed. The relationships between path dependency and equilibrium, and path dependency and fundamental uncertainty are also discussed. Finally, a typology of dynamical systems is developed to clarify these relationships.

  13. A Pareto-Based Adaptive Variable Neighborhood Search for Biobjective Hybrid Flow Shop Scheduling Problem with Sequence-Dependent Setup Time

    Directory of Open Access Journals (Sweden)

    Huixin Tian

    2016-01-01

    Full Text Available Different from most researches focused on the single objective hybrid flowshop scheduling (HFS problem, this paper investigates a biobjective HFS problem with sequence dependent setup time. The two objectives are the minimization of total weighted tardiness and the total setup time. To efficiently solve this problem, a Pareto-based adaptive biobjective variable neighborhood search (PABOVNS is developed. In the proposed PABOVNS, a solution is denoted as a sequence of all jobs and a decoding procedure is presented to obtain the corresponding complete schedule. In addition, the proposed PABOVNS has three major features that can guarantee a good balance of exploration and exploitation. First, an adaptive selection strategy of neighborhoods is proposed to automatically select the most promising neighborhood instead of the sequential selection strategy of canonical VNS. Second, a two phase multiobjective local search based on neighborhood search and path relinking is designed for each selected neighborhood. Third, an external archive with diversity maintenance is adopted to store the nondominated solutions and at the same time provide initial solutions for the local search. Computational results based on randomly generated instances show that the PABOVNS is efficient and even superior to some other powerful multiobjective algorithms in the literature.

  14. Variable temperature ion trap studies of CH4+ + H2, HD and D2: negative temperature dependence and significant isotope effect

    International Nuclear Information System (INIS)

    Asvany, O.; Savic, I.; Schlemmer, S.; Gerlich, D.

    2004-01-01

    Reactions of methane cations, CH 4 + , with H 2 , HD and D 2 have been studied in a variable temperature 22-pole ion trap from room temperature down to 15 K. The formation of CH 5 + in collisions with H 2 is slow at 300 K, but it becomes faster by at least one order of magnitude when the temperature is lowered to 15 K. This behavior is tentatively explained with a longer complex lifetime at low temperatures. However, since tunneling is most probably not responsible for product formation, other dynamical or statistical restrictions must be responsible for the negative temperature dependence. In collisions of CH 4 + with HD, the CH 5 + product ion (68% at 15 K) prevails over CH 4 D + (32%). Reaction of CH 4 + with D 2 is found to be much slower than with H 2 or HD. The rate coefficient for converting CH 4 + into CH 3 D + by H-D exchange has been determined to be smaller than 10 -12 cm 3 /s, indicating that scrambling in the CH 6 + complex is very unlikely

  15. Variable temperature ion trap studies of CH{sub 4}{sup +} + H{sub 2}, HD and D{sub 2}: negative temperature dependence and significant isotope effect

    Energy Technology Data Exchange (ETDEWEB)

    Asvany, O.; Savic, I.; Schlemmer, S.; Gerlich, D

    2004-03-08

    Reactions of methane cations, CH{sub 4}{sup +}, with H{sub 2}, HD and D{sub 2} have been studied in a variable temperature 22-pole ion trap from room temperature down to 15 K. The formation of CH{sub 5}{sup +} in collisions with H{sub 2} is slow at 300 K, but it becomes faster by at least one order of magnitude when the temperature is lowered to 15 K. This behavior is tentatively explained with a longer complex lifetime at low temperatures. However, since tunneling is most probably not responsible for product formation, other dynamical or statistical restrictions must be responsible for the negative temperature dependence. In collisions of CH{sub 4}{sup +} with HD, the CH{sub 5}{sup +} product ion (68% at 15 K) prevails over CH{sub 4}D{sup +} (32%). Reaction of CH{sub 4}{sup +} with D{sub 2} is found to be much slower than with H{sub 2} or HD. The rate coefficient for converting CH{sub 4}{sup +} into CH{sub 3}D{sup +} by H-D exchange has been determined to be smaller than 10{sup -12} cm{sup 3}/s, indicating that scrambling in the CH{sub 6}{sup +} complex is very unlikely.

  16. PsbS-specific zeaxanthin-independent changes in fluorescence emission spectrum as a signature of energy-dependent non-photochemical quenching in higher plants.

    Science.gov (United States)

    Zulfugarov, Ismayil S; Tovuu, Altanzaya; Dogsom, Bolormaa; Lee, Chung Yeol; Lee, Choon-Hwan

    2010-05-01

    The PsbS protein of photosystem II is necessary for the development of energy-dependent quenching of chlorophyll (Chl) fluorescence (qE), and PsbS-deficient Arabidopsis plant leaves failed to show qE-specific changes in the steady-state 77 K fluorescence emission spectra observed in wild-type leaves. The difference spectrum between the quenched and un-quenched states showed a negative peak at 682 nm. Although the level of qE development in the zeaxanthin-less npq1-2 mutant plants, which lacked violaxanthin de-epoxidase enzyme, was only half that of wild type, there were no noticeable changes in this qE-dependent difference spectrum. This zeaxanthin-independent DeltaF682 signal was not dependent on state transition, and the signal was not due to photobleaching of pigments either. These results suggest that DeltaF682 signal is formed due to PsbS-specific conformational changes in the quenching site of qE and is a new signature of qE generation in higher plants.

  17. Can a soda-lime glass be used to demonstrate how patterns of strength dependence are influenced by pre-cementation and resin-cementation variables?

    LENUS (Irish Health Repository)

    Hooi, Paul

    2013-01-01

    To determine how the variability in biaxial flexure strength of a soda-lime glass analogue for a PLV and DBC material was influenced by precementation operative variables and following resin-cement coating.

  18. CD1d-dependent NKT cells play a protective role in acute and chronic arthritis models by ameliorating antigen-specific Th1 responses

    DEFF Research Database (Denmark)

    Teige, Anna; Bockermann, Robert; Hasan, Maruf

    2010-01-01

    -induced arthritis (AIA) and collagen-induced arthritis (CIA), to evaluate acute and chronic arthritis in CD1d knockout mice and mice depleted of NK1.1(+) cells. CD1d-deficient mice developed more severe AIA compared with wild-type littermates, with a higher degree of inflammation and proteoglycan depletion. Chronic...... arthritis in CIA was also worse in the absence of CD1d-dependent NKTs. Elevated levels of Ag-specific IFN-gamma production accompanied these findings rather than changes in IL-17alpha. Depletion of NK1.1(+) cells supported these findings in AIA and CIA. This report provides support for CD1d-dependent NKTs...

  19. Brain-specific inactivation of the Crhr1 gene inhibits post-dependent and stress-induced alcohol intake, but does not affect relapse-like drinking

    DEFF Research Database (Denmark)

    Molander, Anna; Vengeliene, Valentina; Heilig, Markus

    2012-01-01

    , a conditional brain-specific Crhr1-knockout (Crhr1(NestinCre)) and a global knockout mouse line were studied for basal alcohol drinking, stress-induced alcohol consumption, deprivation-induced intake, and escalated alcohol consumption in the post-dependent state. In a second set of experiments, we tested CRHR1...... not affect relapse-like drinking after a deprivation period in rats. We conclude that CRH/CRHR1 extra-HPA and HPA signaling may have opposing effects on stress-related alcohol consumption. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load.......Corticotropin-releasing hormone (CRH) and its receptor, CRH receptor-1 (CRHR1), have a key role in alcoholism. Especially, post-dependent and stress-induced alcohol intake involve CRH/CRHR1 signaling within extra-hypothalamic structures, but a contribution of the hypothalamic-pituitary-adrenal (HPA...

  20. In vivo positron emission tomography imaging with [{sup 11}C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons

    Energy Technology Data Exchange (ETDEWEB)

    DeLorenzo, Christine; Brennan, Kathleen G. [Columbia University College of Physicians and Surgeons, Division of Molecular Imaging and Neuropathology, Department of Psychiatry, NYSPI Mail Unit 42, New York, NY (United States); Milak, Matthew S.; Parsey, Ramin V. [Columbia University College of Physicians and Surgeons, Division of Molecular Imaging and Neuropathology, Department of Psychiatry, NYSPI Mail Unit 42, New York, NY (United States); New York State Psychiatric Institute, New York, NY (United States); Kumar, J.S.D.; Mann, J.J. [Columbia University College of Physicians and Surgeons, Division of Molecular Imaging and Neuropathology, Department of Psychiatry, NYSPI Mail Unit 42, New York, NY (United States); New York State Psychiatric Institute, New York, NY (United States); Columbia University College of Physicians and Surgeons, Department of Radiology, New York, NY (United States)

    2011-06-15

    Metabotropic glutamate receptor subtype 5 (mGluR5) dysfunction has been implicated in several disorders. [{sup 11}C]ABP688, a positron emission tomography (PET) ligand targeting mGluR5, could be a valuable tool in the development of novel therapeutics for these disorders by establishing in vivo drug occupancy. Due to safety concerns in humans, these studies may be performed in nonhuman primates. Therefore, in vivo characterization of [{sup 11}C]ABP688 in nonhuman primates is essential. Test-retest studies were performed in baboons (Papio anubis) to compare modeling approaches and determine the optimal reference region. The mGluR5-specific antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) was then used in test-block studies, in which ligand binding was measured before and after MTEP administration. Test/block data were analyzed both by calculating changes in binding and using a graphical approach, which allowed estimation of both MTEP occupancy and nonspecific binding. Test-retest results, which have not been previously reported for [{sup 11}C]ABP688, indicated that [{sup 11}C]ABP688 variability is low using an unconstrained two-tissue compartment model. The most appropriate, though not ideal, reference region was found to be the gray matter of the cerebellum. Using these optimal modeling techniques on the test/block data, about 90% occupancy was estimated by the graphical approach. These studies are the first to demonstrate the specificity of [{sup 11}C]ABP688 for mGluR5 with in vivo PET in nonhuman primates. The results indicate that, in baboons, occupancy of mGluR5 is detectable by in vivo PET, a useful finding for proceeding to human studies, or performing further baboon studies, quantifying the in vivo occupancy of novel therapeutics targeting mGluR5. (orig.)

  1. pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-β peptide

    International Nuclear Information System (INIS)

    Ghalebani, Leila; Wahlström, Anna; Danielsson, Jens; Wärmländer, Sebastian K.T.S.; Gräslund, Astrid

    2012-01-01

    Highlights: ► Cu(II) and Zn(II) display pH-dependent binding to the Aβ(1–40) peptide. ► At pH 7.4 both metal ions display residue-specific binding to the Aβ peptide. ► At pH 5.5 the binding specificity is lost for Zn(II). ► Differential Cu(II) and Zn(II) binding may help explain metal-induced AD toxicity. -- Abstract: Metal ions like Cu(II) and Zn(II) are accumulated in Alzheimer’s disease amyloid plaques. The amyloid-β (Aβ) peptide involved in the disease interacts with these metal ions at neutral pH via ligands provided by the N-terminal histidines and the N-terminus. The present study uses high-resolution NMR spectroscopy to monitor the residue-specific interactions of Cu(II) and Zn(II) with 15 N- and 13 C, 15 N-labeled Aβ(1–40) peptides at varying pH levels. At pH 7.4 both ions bind to the specific ligands, competing with one another. At pH 5.5 Cu(II) retains its specific histidine ligands, while Zn(II) seems to lack residue-specific interactions. The low pH mimics acidosis which is linked to inflammatory processes in vivo. The results suggest that the cell toxic effects of redox active Cu(II) binding to Aβ may be reversed by the protective activity of non-redox active Zn(II) binding to the same major binding site under non-acidic conditions. Under acidic conditions, the protective effect of Zn(II) may be decreased or changed, since Zn(II) is less able to compete with Cu(II) for the specific binding site on the Aβ peptide under these conditions.

  2. NMDAR NR2A and NR2B specific PKC-dependent regulation of mGluR is defective in the Fragile X Syndrome mouse model

    DEFF Research Database (Denmark)

    Banke, Tue G.; Toft, Anna Karina; Lundbye, Camilla Johanne

    The Fragile X Syndrome (FXS) animal model, the Fmr1 knock-out (KO) mouse, has demonstrated an increased mGluR5-mediated long-term depression (LTD). However, surprisingly little information exists about other ion channels/receptors and their effects on FXS, including NMDA receptors (NMDAR). Here we....... Furthermore, in this model it appears that NR2B activation stimulates PKC, while NR2A activation halts or reverses this effect. In addition, in the KO mice, the coupling between specific NMDAR subunits and mGluR-LTD activity through PKC seems defective in an age-dependent manner. These findings suggest strong...

  3. The dynamic relationship between current and previous severe hypoglycemic events: a lagged dependent variable analysis among patients with type 2 diabetes who have initiated basal insulin.

    Science.gov (United States)

    Ganz, Michael L; Li, Qian; Wintfeld, Neil S; Lee, Yuan-Chi; Sorli, Christopher; Huang, Joanna C

    2015-01-01

    Past studies have found episodes of severe hypoglycemia (SH) to be serially dependent. Those studies, however, only considered the impact of a single (index) event on future risk; few have analyzed SH risk as it evolves over time in the presence (or absence) of continuing events. The objective of this study was to determine the dynamic risks of SH events conditional on preceding SH events among patients with type 2 diabetes (T2D) who have initiated basal insulin. We used an electronic health records database from the United States that included encounter and laboratory data and clinical notes on T2D patients who initiated basal insulin therapy between 2008 and 2011 and to identify SH events. We used a repeated-measures lagged dependent variable logistic regression model to estimate the impact of SH in one quarter on the risk of SH in the next quarter. We identified 7235 patients with T2D who initiated basal insulin. Patients who experienced ≥1 SH event during any quarter were more likely to have ≥1 SH event during the subsequent quarter than those who did not (predicted probabilities of 7.4% and 1.0%, respectively; p history of SH before starting basal insulin (predicted probabilities of 1.0% and 3.2%, respectively; p history of SH during the titration period (predicted probabilities of 1.1% and 2.8%, respectively; p history of SH events and therefore the value of preventing one SH event may be substantial. These results can inform patient care by providing clinicians with dynamic data on a patient's risk of SH, which in turn can facilitate appropriate adjustment of the risk-benefit ratio for individualized patient care. These results should, however, be interpreted in light of the key limitations of our study: not all SH events may have been captured or coded in the database, data on filled prescriptions were not available, we were unable to adjust for basal insulin dose, and the post-titration follow-up period could have divided into time units other

  4. Regulation of AKT phosphorylation at Ser473 and Thr308 by endoplasmic reticulum stress modulates substrate specificity in a severity dependent manner.

    Directory of Open Access Journals (Sweden)

    Hong Wa Yung

    2011-03-01

    Full Text Available Endoplasmic reticulum (ER stress is a common factor in the pathophysiology of diverse human diseases that are characterised by contrasting cellular behaviours, from proliferation in cancer to apoptosis in neurodegenerative disorders. Coincidently, dysregulation of AKT/PKB activity, which is the central regulator of cell growth, proliferation and survival, is often associated with the same diseases. Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets. ER stress also reduces both total and phosphorylated AKT in a severity-dependent manner, without affecting activity of the upstream kinase PDK1. Normalisation to total AKT revealed that under ER stress phosphorylation of Thr308 is suppressed while that of Ser473 is increased. ER stress induces GRP78, and siRNA-mediated knock-down of GRP78 enhances phosphorylation at Ser473 by 3.6 fold, but not at Thr308. Substrate specificity is again altered. An in-situ proximity ligation assay revealed a physical interaction between GRP78 and AKT at the plasma membrane of cells following induction of ER stress. Staining was weak in cells with normal nuclear morphology but stronger in those displaying rounded, condensed nuclei. Co-immunoprecipitation of GRP78 and P-AKT(Ser473 confirmed the immuno-complex consists of non-phosphorylated AKT (Ser473 and Thr308. The interaction is likely specific as AKT did not bind to all molecular chaperones, and GRP78 did not bind to p70 S6 kinase. These findings provide one mechanistic explanation for how ER stress contributes to human pathologies demonstrating contrasting cell fates via modulation of AKT signalling.

  5. Regulation of AKT Phosphorylation at Ser473 and Thr308 by Endoplasmic Reticulum Stress Modulates Substrate Specificity in a Severity Dependent Manner

    Science.gov (United States)

    Yung, Hong Wa

    2011-01-01

    Endoplasmic reticulum (ER) stress is a common factor in the pathophysiology of diverse human diseases that are characterised by contrasting cellular behaviours, from proliferation in cancer to apoptosis in neurodegenerative disorders. Coincidently, dysregulation of AKT/PKB activity, which is the central regulator of cell growth, proliferation and survival, is often associated with the same diseases. Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets. ER stress also reduces both total and phosphorylated AKT in a severity-dependent manner, without affecting activity of the upstream kinase PDK1. Normalisation to total AKT revealed that under ER stress phosphorylation of Thr308 is suppressed while that of Ser473 is increased. ER stress induces GRP78, and siRNA-mediated knock-down of GRP78 enhances phosphorylation at Ser473 by 3.6 fold, but not at Thr308. Substrate specificity is again altered. An in-situ proximity ligation assay revealed a physical interaction between GRP78 and AKT at the plasma membrane of cells following induction of ER stress. Staining was weak in cells with normal nuclear morphology but stronger in those displaying rounded, condensed nuclei. Co-immunoprecipitation of GRP78 and P-AKT(Ser473) confirmed the immuno-complex consists of non-phosphorylated AKT (Ser473 and Thr308). The interaction is likely specific as AKT did not bind to all molecular chaperones, and GRP78 did not bind to p70 S6 kinase. These findings provide one mechanistic explanation for how ER stress contributes to human pathologies demonstrating contrasting cell fates via modulation of AKT signalling. PMID:21445305

  6. Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension.

    Science.gov (United States)

    Ueda, Kohei; Nishimoto, Mitsuhiro; Hirohama, Daigoro; Ayuzawa, Nobuhiro; Kawarazaki, Wakako; Watanabe, Atsushi; Shimosawa, Tatsuo; Loffing, Johannes; Zhang, Ming-Zhi; Marumo, Takeshi; Fujita, Toshiro

    2017-07-01

    Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl - cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl - cotransporter phosphorylation. Accordingly, a Na + -Cl - cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl - cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na + -Cl - cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the

  7. Community and species-specific responses of wild bees to insect pest control programs applied to a pollinator-dependent crop.

    Science.gov (United States)

    Tuell, Julianna K; Isaacs, Rufus

    2010-06-01

    Wild bee conservation is regarded as essential for sustainable production of pollinator-dependent crops, yet little is known about the effects on wild bee communities of typical insect pest management programs used postbloom. We developed an insecticide program risk (IPR) index to quantify the relative risk to wild bees of insecticide programs applied to blueberry fields. This was used to determine the relationship between IPR and the abundance, diversity, and richness of wild bee communities sampled during three successive flowering seasons. In 2 of 3 yr, bee abundance and species richness declined with increasing IPR. Bee diversity declined with IPR in one of 3 yr. These results indicate that wild bee communities are negatively affected by increasingly intensive chemical pest management activities in crop fields and that interyear variability in bee populations has the potential to mask such effects in short-term studies. When several wild bee species were analyzed separately, two of three solitary and one of three social blueberry-foraging species declined with increasing IPR values, suggesting that different life histories and nesting habits may help some bee populations escape the negative effects of insecticides applied after bloom. Pollinator conservation programs aimed strictly at reducing insecticide use may have varying success, depending on the biology of the target bee species. The IPR index provides a standard method to compare pest management programs for their potential effect on wild bee communities, with broad application for use in other agricultural systems.

  8. Land-use regression with long-term satellite-based greenness index and culture-specific sources to model PM2.5 spatial-temporal variability.

    Science.gov (United States)

    Wu, Chih-Da; Chen, Yu-Cheng; Pan, Wen-Chi; Zeng, Yu-Ting; Chen, Mu-Jean; Guo, Yue Leon; Lung, Shih-Chun Candice

    2017-05-01

    This study utilized a long-term satellite-based vegetation index, and considered culture-specific emission sources (temples and Chinese restaurants) with Land-use Regression (LUR) modelling to estimate the spatial-temporal variability of PM 2.5 using data from Taipei metropolis, which exhibits typical Asian city characteristics. Annual average PM 2.5 concentrations from 2006 to 2012 of 17 air quality monitoring stations established by Environmental Protection Administration of Taiwan were used for model development. PM 2.5 measurements from 2013 were used for external data verification. Monthly Normalized Difference Vegetation Index (NDVI) images coupled with buffer analysis were used to assess the spatial-temporal variations of greenness surrounding the monitoring sites. The distribution of temples and Chinese restaurants were included to represent the emission contributions from incense and joss money burning, and gas cooking, respectively. Spearman correlation coefficient and stepwise regression were used for LUR model development, and 10-fold cross-validation and external data verification were applied to verify the model reliability. The results showed a strongly negative correlation (r: -0.71 to -0.77) between NDVI and PM 2.5 while temples (r: 0.52 to 0.66) and Chinese restaurants (r: 0.31 to 0.44) were positively correlated to PM 2.5 concentrations. With the adjusted model R 2 of 0.89, a cross-validated adj-R 2 of 0.90, and external validated R 2 of 0.83, the high explanatory power of the resultant model was confirmed. Moreover, the averaged NDVI within a 1750 m circular buffer (p < 0.01), the number of Chinese restaurants within a 1750 m buffer (p < 0.01), and the number of temples within a 750 m buffer (p = 0.06) were selected as important predictors during the stepwise selection procedures. According to the partial R 2 , NDVI explained 66% of PM 2.5 variation and was the dominant variable in the developed model. We suggest future studies

  9. Twelve-Month Prostate-Specific Antigen Values and Perineural Invasion as Strong Independent Prognostic Variables of Long-Term Biochemical Outcome After Prostate Seed Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ding, William, E-mail: billyding888@gmail.com [Department of Radiation Oncology, California Pacific Medical Center, San Francisco, California (United States); Lee, John [Department of Radiation Oncology, California Pacific Medical Center, San Francisco, California (United States); Chamberlain, David [Department of Radiation Oncology, St. Mary' s Regional Medical Center, Reno, Nevada (United States); Cunningham, James [Carson Urology, Carson City, Nevada (United States); Yang Lixi [Department of Radiation Oncology, California Pacific Medical Center, San Francisco, California (United States); Tay, Jonathan [Department of Radiation Oncology, St. Mary' s Regional Medical Center, Reno, Nevada (United States)

    2012-11-15

    Purpose: To determine whether post-treatment prostate-specific antigen (ptPSA) values at 12 months and other clinical parameters predict long-term PSA relapse-free survival (PRFS) following prostate seed brachytherapy. Methods and Materials: Records of 204 hormone-naieve patients with localized adenocarcinoma of the prostate treated at St. Mary's Regional Medical Center in Reno, NV, and at Carson Tahoe Regional Medical Center in Carson City, NV, between 1998 and 2003, using I-125 or Pd-103 seed brachytherapy, were retrospectively analyzed. Treatment planning was done using a preplanned, modified peripheral loading technique. A total of 185 of 204 patients had PSA records at 12 months after implant. Variables included were age, initial pretreatment PSA, Gleason score, T stage, National Comprehensive Cancer Network (NCCN) risk group (RG), perineural invasion (PNI), external beam boost, dose, and ptPSA levels at 12 months with cutpoints at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml. Results: Median follow-up was 80 months, and median age was 69 years. The numbers of patients stratified by NCCN low, intermediate, and high RG were 110:65:10, respectively. Monotherapy and boost prescription doses were 145 Gy and 110 Gy for I-125, and 125 Gy and 100 Gy for Pd-103 seeds, respectively. The median dose (D90) was 95.4% of the prescribed dose. The 5-year PRFS at the 12-months ptPSA levels of {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml were 98.5%, 85.7%, 61.5%, and 22.2%, respectively. The 10-year PRFS at the 12-months ptPSA levels of {<=}1 and 1.01 to 2.00 ng/ml were 90.5% and 85.7%, respectively. In multivariate analysis, both ptPSA and PNI were significant independent predictors of PRFS. Hazard ratios (HR) for ptPSA levels at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml at 12 months were 1, 4.96, 27.57, and 65.10, respectively. PNI had an HR of 6.1 (p = 0.009). Conclusions: Presence of PNI and ptPSA values at 12 months are strong prognostic

  10. Twelve-Month Prostate-Specific Antigen Values and Perineural Invasion as Strong Independent Prognostic Variables of Long-Term Biochemical Outcome After Prostate Seed Brachytherapy

    International Nuclear Information System (INIS)

    Ding, William; Lee, John; Chamberlain, David; Cunningham, James; Yang Lixi; Tay, Jonathan

    2012-01-01

    Purpose: To determine whether post-treatment prostate-specific antigen (ptPSA) values at 12 months and other clinical parameters predict long-term PSA relapse-free survival (PRFS) following prostate seed brachytherapy. Methods and Materials: Records of 204 hormone-naïve patients with localized adenocarcinoma of the prostate treated at St. Mary’s Regional Medical Center in Reno, NV, and at Carson Tahoe Regional Medical Center in Carson City, NV, between 1998 and 2003, using I-125 or Pd-103 seed brachytherapy, were retrospectively analyzed. Treatment planning was done using a preplanned, modified peripheral loading technique. A total of 185 of 204 patients had PSA records at 12 months after implant. Variables included were age, initial pretreatment PSA, Gleason score, T stage, National Comprehensive Cancer Network (NCCN) risk group (RG), perineural invasion (PNI), external beam boost, dose, and ptPSA levels at 12 months with cutpoints at ≤1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml. Results: Median follow-up was 80 months, and median age was 69 years. The numbers of patients stratified by NCCN low, intermediate, and high RG were 110:65:10, respectively. Monotherapy and boost prescription doses were 145 Gy and 110 Gy for I-125, and 125 Gy and 100 Gy for Pd-103 seeds, respectively. The median dose (D90) was 95.4% of the prescribed dose. The 5-year PRFS at the 12-months ptPSA levels of ≤1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml were 98.5%, 85.7%, 61.5%, and 22.2%, respectively. The 10-year PRFS at the 12-months ptPSA levels of ≤1 and 1.01 to 2.00 ng/ml were 90.5% and 85.7%, respectively. In multivariate analysis, both ptPSA and PNI were significant independent predictors of PRFS. Hazard ratios (HR) for ptPSA levels at ≤1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml at 12 months were 1, 4.96, 27.57, and 65.10, respectively. PNI had an HR of 6.1 (p = 0.009). Conclusions: Presence of PNI and ptPSA values at 12 months are strong prognostic variables for

  11. Leukocyte function-associated antigen-1-dependent lysis of Fas+ (CD95+/Apo-1+) innocent bystanders by antigen-specific CD8+ CTL.

    Science.gov (United States)

    Kojima, H; Eshima, K; Takayama, H; Sitkovsky, M V

    1997-09-15

    Exquisite specificity toward Ag-bearing cells (cognate targets) is one of the most important properties of CD8+ CTL-mediated cytotoxicity. Using highly Ag-specific CD8+ CTL lines and clones, which spare noncognate, Ag-free targets, we found that in the presence of Ag-bearing targets the CTL acquire the ability to lyse noncognate target cells (bystanders). It is shown that the unexpectedly rapid and efficient lysis of bystanders by Ag-activated CTL is mediated by a Fas ligand (FasL)/Fas-based mechanism and does not depend on perforin. The CTL lysed Fas-expressing bystanders, but spared the Fas-negative or anti-Fas mAb-resistant bystander cells. Accordingly, the FasL-deficient gld/gld CTL did not kill bystanders, while perforin-deficient CTL did. Unlike anti-Fas mAb-induced cell death, the lysis of bystanders was not only FasL/Fas dependent but also required adhesion molecule LFA-1 on the surface of the activated CTL. Lysis of bystanders is viewed as acceptable "collateral" damage, but the persistent presence of activated CTL could result in immunopathologies involving functional Fas-expressing tissues.

  12. Hip shape is symmetric, non-dependent on limb dominance and gender-specific. Implications for femoroacetabular impingement. A 3D CT analysis in asymptomatic subjects

    International Nuclear Information System (INIS)

    Mascarenhas, Vasco V.; Rego, Paulo; Dantas, Pedro; Castro, Miguel; Jans, Lennart; Marques, Rui M.; Gouveia, Nelia; Consciencia, Jose G.; Soldado, Francisco; Ayeni, Olufemi R.

    2018-01-01

    To determine the reference intervals (RefInt) of the quantitative morphometric parameters of femoroacetabular impingement (FAI) in asymptomatic hips with computed tomography (CT) and determine their dependence on age, side, limb dominance and sex. We prospectively included 590 patients and evaluated 1111 hips with semi-automated CT analysis. We calculated overall, side- and sex-specific parameters for imaging signs of cam [omega and alpha angle (α )] and pincer-type morphology [acetabular version (ACvers), lateral centre-edge angle (LCEA) and cranio-caudal coverage]. Hip shape was symmetrical and did not depend on limb dominance. The 95% RefInt limits were sex-different for all cam-type parameters and extended beyond current abnormal thresholds. Specifically, the upper limits of RefInt for α at 12:00, 1:30 and 3:00 o'clock positions were 56 , 70 and 58 , respectively, and 45 for LCEA. Acetabular morphology varied between age groups, with a trend toward an LCEA/ACvers increase over time. Our morphometric measurements can be used to estimate normal hip morphology in asymptomatic individuals. Notably they extended beyond current thresholds used for FAI imaging diagnosis, which was most pronounced for cam-type parameters. We suggest the need to reassess α RefInt and consider a 60 threshold for the 12:00/3:00 positions and 65-70 for other antero-superior positions. (orig.)

  13. PRDM16 enhances nuclear receptor-dependent transcription of the brown fat-specific Ucp1 gene through interactions with Mediator subunit MED1.

    Science.gov (United States)

    Iida, Satoshi; Chen, Wei; Nakadai, Tomoyoshi; Ohkuma, Yoshiaki; Roeder, Robert G

    2015-02-01

    PR domain-containing 16 (PRDM16) induces expression of brown fat-specific genes in brown and beige adipocytes, although the underlying transcription-related mechanisms remain largely unknown. Here, in vitro studies show that PRDM16, through its zinc finger domains, directly interacts with the MED1 subunit of the Mediator complex, is recruited to the enhancer of the brown fat-specific uncoupling protein 1 (Ucp1) gene through this interaction, and enhances thyroid hormone receptor (TR)-driven transcription in a biochemically defined system in a Mediator-dependent manner, thus providing a direct link to the general transcription machinery. Complementary cell-based studies show that upon forskolin treatment, PRDM16 induces Ucp1 expression in undifferentiated murine embryonic fibroblasts, that this induction depends on MED1 and TR, and, consistent with a direct effect, that PRDM16 is recruited to the Ucp1 enhancer. Related studies have defined MED1 and PRDM16 interaction domains important for Ucp1 versus Ppargc1a induction by PRDM16. These results reveal novel mechanisms for PRDM16 function through the Mediator complex. © 2015 Iida et al.; Published by Cold Spring Harbor Laboratory Press.

  14. Surfing wave climate variability

    Science.gov (United States)

    Espejo, Antonio; Losada, Iñigo J.; Méndez, Fernando J.

    2014-10-01

    International surfing destinations are highly dependent on specific combinations of wind-wave formation, thermal conditions and local bathymetry. Surf quality depends on a vast number of geophysical variables, and analyses of surf quality require the consideration of the seasonal, interannual and long-term variability of surf conditions on a global scale. A multivariable standardized index based on expert judgment is proposed for this purpose. This index makes it possible to analyze surf conditions objectively over a global domain. A summary of global surf resources based on a new index integrating existing wave, wind, tides and sea surface temperature databases is presented. According to general atmospheric circulation and swell propagation patterns, results show that west-facing low to middle-latitude coasts are more suitable for surfing, especially those in the Southern Hemisphere. Month-to-month analysis reveals strong seasonal variations in the occurrence of surfable events, enhancing the frequency of such events in the North Atlantic and the North Pacific. Interannual variability was investigated by comparing occurrence values with global and regional modes of low-frequency climate variability such as El Niño and the North Atlantic Oscillation, revealing their strong influence at both the global and the regional scale. Results of the long-term trends demonstrate an increase in the probability of surfable events on west-facing coasts around the world in recent years. The resulting maps provide useful information for surfers, the surf tourism industry and surf-related coastal planners and stakeholders.

  15. FasL and FADD delivery by a glioma-specific and cell cycle-dependent HSV-1 amplicon virus enhanced apoptosis in primary human brain tumors

    Directory of Open Access Journals (Sweden)

    Lam Paula Y

    2010-10-01

    Full Text Available Abstract Background Glioblastoma multiforme is the most malignant cancer of the brain and is notoriously difficult to treat due to the highly proliferative and infiltrative nature of the cells. Herein, we explored the combination treatment of pre-established human glioma xenograft using multiple therapeutic genes whereby the gene expression is regulated by both cell-type and cell cycle-dependent transcriptional regulatory mechanism conferred by recombinant HSV-1 amplicon vectors. Results We demonstrated for the first time that Ki67-positive proliferating primary human glioma cells cultured from biopsy samples were effectively induced into cell death by the dual-specific function of the pG8-FasL amplicon vectors. These vectors were relatively stable and exhibited minimal cytotoxicity in vivo. Intracranial implantation of pre-transduced glioma cells resulted in better survival outcome when compared with viral vectors inoculated one week post-implantation of tumor cells, indicating that therapeutic efficacy is dependent on the viral spread and mode of viral vectors administration. We further showed that pG8-FasL amplicon vectors are functional in the presence of commonly used treatment regimens for human brain cancer. In fact, the combined therapies of pG8-FasL and pG8-FADD in the presence of temozolomide significantly improved the survival of mice bearing intracranial high-grade gliomas. Conclusion Taken together, our results showed that the glioma-specific and cell cycle-dependent HSV-1 amplicon vector is potentially useful as an adjuvant therapy to complement the current gene therapy strategy for gliomas.

  16. Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life.

    Science.gov (United States)

    Xiong, Weili; Brown, Christopher T; Morowitz, Michael J; Banfield, Jillian F; Hettich, Robert L

    2017-07-10

    Establishment of the human gut microbiota begins at birth. This early-life microbiota development can impact host physiology during infancy and even across an entire life span. However, the functional stability and population structure of the gut microbiota during initial colonization remain poorly understood. Metaproteomics is an emerging technology for the large-scale characterization of metabolic functions in complex microbial communities (gut microbiota). We applied a metagenome-informed metaproteomic approach to study the temporal and inter-individual differences of metabolic functions during microbial colonization of preterm human infants' gut. By analyzing 30 individual fecal samples, we identified up to 12,568 protein groups for each of four infants, including both human and microbial proteins. With genome-resolved matched metagenomics, proteins were confidently identified at the species/strain level. The maximum percentage of the proteome detected for the abundant organisms was ~45%. A time-dependent increase in the relative abundance of microbial versus human proteins suggested increasing microbial colonization during the first few weeks of early life. We observed remarkable variations and temporal shifts in the relative protein abundances of each organism in these preterm gut communities. Given the dissimilarity of the communities, only 81 microbial EggNOG orthologous groups and 57 human proteins were observed across all samples. These conserved microbial proteins were involved in carbohydrate, energy, amino acid and nucleotide metabolism while conserved human proteins were related to immune response and mucosal maturation. We identified seven proteome clusters for the communities and showed infant gut proteome profiles were unstable across time and not individual-specific. Applying a gut-specific metabolic module (GMM) analysis, we found that gut communities varied primarily in the contribution of nutrient (carbohydrates, lipids, and amino acids

  17. Influence of specific individual and environmental variables on the relationship between body mass index and health-related quality of life in overweight and obese adolescents.

    Science.gov (United States)

    Kolodziejczyk, Julia K; Gutzmer, Kyle; Wright, Shana M; Arredondo, Elva M; Hill, Linda; Patrick, Kevin; Huang, Jeannie S; Gottschalk, Michael; Norman, Gregory J

    2015-01-01

    Overweight and obese adolescents are at risk for low health-related quality of life (HRQOL). We examined the role of individual- and environmental-level variables on the relationship between body mass index (BMI kg/m(2)) and HRQOL in adolescents. Linear regressions were performed to conduct mediation and moderation analyses on the relationship between BMI and HRQOL in overweight and obese adolescents (N = 205). HRQOL was measured by the Pediatric Quality of Life Inventory. Hypothesized mediators included depression, measured by the Center for Epidemiologic Studies Depression Scale; body image, measured by the gender-specific body dissatisfaction subscale of the Eating Disorder Inventory; and self-esteem, measured by the Rosenberg Self-Esteem Scale. Mediation was assessed using Baron and Kenny's approach and Sobel's test of indirect effects. Anglo-acculturation, measured by the Short Acculturation Scale for Hispanics-Youth, and environmental perception, measured by parent-proxy report of the Neighborhood Environment Walkability Scale, were hypothesized moderators. Body image mediated the relationship between BMI and HRQOL (b = -0.34, SE = 0.17, adj R (2) = 0.19, p = .051), and self-esteem was a partial mediator (b = -0.37, SE = 0.17, adj R (2) = 0.24, p = .027). Sobel's test confirmed these results (p moderation effects were found. The finding that individual-level factors, such as body image and self-esteem, influence the relationship between BMI and HRQOL while environmental factors, such as neighborhood environment and acculturation, do not extends previous research. The finding that body image and self-esteem partially mediate this relationship presents new areas to investigate in interventions that address BMI in youth.

  18. Intra-specific variability in life-history traits of Anadara tuberculosa (Mollusca: Bivalvia) in the mangrove ecosystem of the Southern coast of Ecuador.

    Science.gov (United States)

    Flores, Luis; Licandeo, Roberto; Cubillos, Luis A; Mora, Elba

    2014-06-01

    Anadara tuberculosa is one of the most important bivalves along the Western Pacific coast because of its commercial value. Nevertheless, the variability in growth, long-life span, natural mortality and reproductive parameters of this mangrove cockle has not yet been described. The aim of this study was to analyze these life-history traits in three areas of the Southern coast of Ecuador. Empirical and length-based methods were used to estimate these biological parameters. Body size data were collected from the commercial fishery between 2004 and 2011 in landing ports near to the Archipelago of Jambeli [Puerto Bolivar (PB), Puerto Jeli (PJ) and Puerto Hualtaco (PH)]. The von Bertalanffy growth parameters for combined sex were estimated between 70.87 to 93.45mm for L(infinity) and 0.22 to 0.80/year for k. The growth indices (PHI') ranged from 3.17 to 3.85, while the overall growth performance (OGP) ranged from 5.03 to 5.82. The mean of long-life span (t(max)), size and age at maturity (L50% and t50%) were estimated in 7.71 +/- 2.53 years, 39.13 +/- 2.24mm and 1.46 +/- 0.56 years for PB; 9.51 +/- 2.85 years, 37.78 +/- 1.95mm and 1.37 +/- 0.41 years for PJ and 5.81 +/- 2.11 years, 39.73 +/- 3.31mm and 0.94 +/- 0.41 years for PH. Natural mortality (M) ranged from 0.46 to 1.28/year. We concluded that significant intra-specific variation was observed in a temporal scale in PHI' and OGP indices as well as L50% and M. Therefore, temporal changes in these life-history traits should be taken into account when assessing the status of the mangrove cockle fishery.

  19. Studies on the concentration dependence of specific rotation of Alpha lactose monohydrate (α-LM) aqueous solutions and growth of α-LM single crystals

    Science.gov (United States)

    Vinodhini, K.; Divya Bharathi, R.; Srinivasan, K.

    2018-02-01

    Lactose is an optically active substance. As it is one of the reducing sugars, exhibits mutarotation in solution when it dissolves in any solvent. In solution, lactose exists in two isomeric forms, alpha-Lactose (α-L) and beta-lactose (β-L) through the mutarotation reaction. Mutarotation produces a dynamic equilibrium between two isomers in a solution and kinetics of this process determines the growth rate of alpha lactose monohydrate (α-LM) crystals. Since no data were available on the specific rotation of aqueous α-LM solutions at different concentrations at 33 °C, the initial experiments were carried out on the specific rotation of aqueous α-LM solutions at different concentrations at 33 °C. The specific rotations of the solutions were decreased with increasing time through the mutarotation reaction. The initial and final (equilibrium) specific rotations of the solutions were determined by using automatic digital polarimeter. The compositions of α and β-L in all prepared solutions were calculated from initial and final optical rotations by the method of Sharp and Doob. The composition of α-L decreased whereas, the composition of β-L increased in solutions with increasing concentration of α-LM at 33 °C. Experimental results revealed that this method could be easily and safely employed to study the dependence of specific rotation of solutions on their concentration. The effect of β-lactose on the morphology of nucleated α-LM single crystals has been studied at different experimental conditions.

  20. Genetic Variability of the Glucose-Dependent Insulinotropic Peptide Gene Is Involved in the Premature Coronary Artery Disease in a Chinese Population with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Xiaowei Ma

    2018-01-01

    Full Text Available Background. Glucose-dependent insulinotropic polypeptide (GIP is closely related to diabetes and obesity, both of which are confirmed to increase the risk of coronary artery disease (CAD. Our study aimed to investigate whether the polymorphisms in GIP genes could affect the risk of cardiovascular disease in type 2 diabetic patients in the Chinese Han population. Methods. We selected and genotyped two haplotype-tagging single nucleotide polymorphisms (tag-SNPs (rs2291725 C>T, rs8078510 G>A of GIP gene based on CHB data in HapMap Phase II database (r2<0.8. The case-control study of Chinese Han population involved 390 diabetic patients with CAD as positive group and 276 diabetic patients without CAD as control group. Allele and genotype frequencies were compared between the two groups. Results. In dominant inheritance model, the carriers of T/T or T/C had a lower risk of CAD (OR = 0.635, 95% CI = 0.463–0.872, p=0.005, even after adjustment other CAD risk factors (gender, age, BMI, smoking status, dyslipidemia, hypertension history, and diabetic duration (OR′ = 0.769, 95% CI′ = 0.626–0.945, p′=0.013. The allele A at rs8078510 was associated with decreased risk of CAD (OR = 0.732, p=0.039. p=0.018 in subgroup analysis, individuals with higher BMI (≥24 kg/m2 had increased risk for CAD when carrying C/C at rs2291725 (OR′ = 1.291, 95% CI′ = 1.017–1.639, p′=0.036. In age < 55 men and age < 65 women, the carriers of allele C at rs2291725 had a higher risk of CAD than noncarriers (OR = 1.627, p=0.015. Carriers of allele G in rs8078510 had higher susceptibility to CAD (OR = 2.049, 95% = CI 1.213–3.463, p=0.007. p=0.004; in addition, allele G in rs8078510 would bring higher CAD risk to the carriers who ever smoked (OR = 1.695, 95% CI = 1.080–2.660, p=0.021. Conclusion. The genetic variability of GIP gene is associated with CAD and it may play a role in the premature CAD in the

  1. Variability of the Cyclin-Dependent Kinase 2 Flexibility Without Significant Change in the Initial Conformation of the Protein or Its Environment; a Computational Study.

    Science.gov (United States)

    Taghizadeh, Mohammad; Goliaei, Bahram; Madadkar-Sobhani, Armin

    2016-06-01

    Protein flexibility, which has been referred as a dynamic behavior has various roles in proteins' functions. Furthermore, for some developed tools in bioinformatics, such as protein-protein docking software, considering the protein flexibility, causes a higher degree of accuracy. Through undertaking the present work, we have accomplished the quantification plus analysis of the variations in the human Cyclin Dependent Kinase 2 (hCDK2) protein flexibility without affecting a significant change in its initial environment or the protein per se. The main goal of the present research was to calculate variations in the flexibility for each residue of the hCDK2, analysis of their flexibility variations through clustering, and to investigate the functional aspects of the residues with high flexibility variations. Using Gromacs package (version 4.5.4), three independent molecular dynamics (MD) simulations of the hCDK2 protein (PDB ID: 1HCL) was accomplished with no significant changes in their initial environments, structures, or conformations, followed by Root Mean Square Fluctuations (RMSF) calculation of these MD trajectories. The amount of variations in these three curves of RMSF was calculated using two formulas. More than 50% of the variation in the flexibility (the distance between the maximum and the minimum amount of the RMSF) was found at the region of Val-154. As well, there are other major flexibility fluctuations in other residues. These residues were mostly positioned in the vicinity of the functional residues. The subsequent works were done, as followed by clustering all hCDK2 residues into four groups considering the amount of their variability with respect to flexibility and their position in the RMSF curves. This work has introduced a new class of flexibility aspect of the proteins' residues. It could also help designing and engineering proteins, with introducing a new dynamic aspect of hCDK2, and accordingly, for the other similar globular proteins. In

  2. All varieties of encoding variability are not created equal: Separating variable processing from variable tasks

    Science.gov (United States)

    Huff, Mark J.; Bodner, Glen E.

    2014-01-01

    Whether encoding variability facilitates memory is shown to depend on whether item-specific and relational processing are both performed across study blocks, and whether study items are weakly versus strongly related. Variable-processing groups studied a word list once using an item-specific task and once using a relational task. Variable-task groups’ two different study tasks recruited the same type of processing each block. Repeated-task groups performed the same study task each block. Recall and recognition were greatest in the variable-processing group, but only with weakly related lists. A variable-processing benefit was also found when task-based processing and list-type processing were complementary (e.g., item-specific processing of a related list) rather than redundant (e.g., relational processing of a related list). That performing both item-specific and relational processing across trials, or within a trial, yields encoding-variability benefits may help reconcile decades of contradictory findings in this area. PMID:25018583

  3. StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

    Energy Technology Data Exchange (ETDEWEB)

    Zemla, A; Lang, D; Kostova, T; Andino, R; Zhou, C

    2010-11-29

    Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory - still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could overcome these difficulties and facilitate the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV, a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus and demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique or that shared structural similarity with structures that are distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected

  4. Oral peptide specific egg antibody to intestinal sodium-dependent phosphate co-transporter-2b is effective at altering phosphate transport in vitro and in vivo.

    Science.gov (United States)

    Bobeck, Elizabeth A; Hellestad, Erica M; Sand, Jordan M; Piccione, Michelle L; Bishop, Jeff W; Helvig, Christian; Petkovich, Martin; Cook, Mark E

    2015-06-01

    Hyperimmunized hens are an effective means of generating large quantities of antigen specific egg antibodies that have use as oral supplements. In this study, we attempted to create a peptide specific antibody that produced outcomes similar to those of the human pharmaceutical, sevelamer HCl, used in the treatment of hyperphosphatemia (a sequela of chronic renal disease). Egg antibodies were generated against 8 different human intestinal sodium-dependent phosphate cotransporter 2b (NaPi2b) peptides, and hNaPi2b peptide egg antibodies were screened for their ability to inhibit phosphate transport in human intestinal Caco-2 cell line. Antibody produced against human peptide sequence TSPSLCWT (anti-h16) was specific for its peptide sequence, and significantly reduced phosphate transport in human Caco-2 cells to 25.3±11.5% of control nonspecific antibody, when compared to nicotinamide, a known inhibitor of phosphate transport (P≤0.05). Antibody was then produced against the mouse-specific peptide h16 counterpart (mouse sequence TSPSYCWT, anti-m16) for further analysis in a murine model. When anti-m16 was fed to mice (1% of diet as dried egg yolk powder), egg yolk immunoglobulin (IgY) was detected using immunohistochemical staining in mouse ileum, and egg anti-m16 IgY colocalized with a commercial goat anti-NaPi2b antibody. The effectiveness of anti-m16 egg antibody in reducing serum phosphate, when compared to sevelamer HCl, was determined in a mouse feeding study. Serum phosphate was reduced 18% (Pegg yolk powder) and 30% (Pegg immunoglobulin. The methods described and the findings reported show that oral egg antibodies are useful and easy to prepare reagents for the study and possible treatment of select diseases. © 2015 Poultry Science Association Inc.

  5. Effective intracellular inhibition of the cAMP-dependent protein kinase by microinjection of a modified form of the specific inhibitor peptide PKi in living fibroblasts.

    Science.gov (United States)

    Fernandez, A; Mery, J; Vandromme, M; Basset, M; Cavadore, J C; Lamb, N J

    1991-08-01

    In order to obtain a peptide retaining its biological activity following microinjection into living cells, we have modified a synthetic peptide [PKi(m)(6-24)], derived from the specific inhibitor protein of the cAMP-dependent protein kinase (A-kinase) in two ways: (1) substitution of the arginine at position 18 for a D-arginine; (2) blockade of the side chain on the C-terminal aspartic acid by a cyclohexyl ester group. In an in vitro assay, PKi(m) has retained a specific inhibitory activity against A-kinase as assessed against six other kinases, with similar efficiency to that of the unmodified PKi(5-24) peptide. Microinjection of PKi(m) into living fibroblasts reveals its capacity to prevent the changes in cell morphology and cytoskeleton induced by drugs which activate endogenous A-kinase, whereas the original PKi peptide failed to do so. This inhibition of A-kinase in vivo by PKi(m) lasts between 4 and 6 h after injection. In light of its effective half-life, this modified peptide opens a route for the use of biologically active peptides in vivo, an approach which has been hampered until now by the exceedingly short half-life of peptides inside living cells. By providing a direct means of inhibiting A-kinase activity for sufficiently long periods to observe effects on cellular functions in living cells, PKi(m) represents a powerful tool in studying the potential role of cAMP-dependent phosphorylation in vivo.

  6. The morphological signs of plants of white cabbage (Brassica oleraceae L. convar. capitata (L. Alef. var. alba DC and their variability depending on type of sort

    Directory of Open Access Journals (Sweden)

    О. Я. Жук

    2008-04-01

    Full Text Available Indicators of the morphological signs of type of sort on white cabbage plants Dutch flat, Belarus, Amager, Langendijker winter and their variability are the presented. It is established low and average factor of a variation at the majority of the morphological signs. Strong high-quality and ecological variability of signs “height external rake” and “its size leafy parts” at type of sort Dutch flat is defined.

  7. Task-specific noise exposure during manual concrete surface grinding in enclosed areas-influence of operation variables and dust control methods.

    Science.gov (United States)

    Akbar-Khanzadeh, Farhang; Ames, April L; Milz, Sheryl A; Akbar-Khanzadeh, Mahboubeh

    2013-01-01

    Noise exposure is a distinct hazard during hand-held concrete grinding activities, and its assessment is challenging because of the many variables involved. Noise dosimeters were used to examine the extent of personal noise exposure while concrete grinding was performed with a variety of grinder sizes, types, accessories, and available dust control methods. Noise monitoring was conducted in an enclosed area covering 52 task-specific grinding sessions lasting from 6 to 72 minutes. Noise levels, either in minute average noise level (Lavg, dBA) or in minute peak (dBC), during concrete grinding were significantly (P grinding cup wheel (blade) sizes of 4-inch (100 mm), 5-inch (125 mm) and 6-inch (150 mm), and surface orientation (horizontal, inclined). Overall, minute Lavg during grinding was 97.0 ± 3.3 (mean ± SD), ranging from 87.9 to 113. The levels of minute Lavg during uncontrolled grinding (98.9 ± 5.2) or wet-grinding (98.5 ± 2.7) were significantly higher than those during local exhaust ventilation (LEV) grinding (96.2 ± 2.8). A 6-inch grinding cup wheel generated significantly higher noise levels (98.7 ± 2.8) than 5-inch (96.3 ± 3.2) or 4-inch (95.3 ± 3.5) cup wheels. The minute peak noise levels (dBC) during grinding was 113 ± 5.2 ranging from 104 to 153. The minute peak noise levels during uncontrolled grinding (119 ± 10.2) were significantly higher than those during wet-grinding (115 ± 4.5) and LEV-grinding (112 ± 3.4). A 6-inch grinding cup wheel generated significantly higher minute peak noise levels (115 ± 5.3) than 5-inch (112 ± 4.5) or 4-inch (111 ± 5.4) cup wheels. Assuming an 8-hour work shift, the results indicated that noise exposure levels during concrete grinding in enclosed areas exceeded the recommended permissible exposure limits and workers should be protected by engineering control methods, safe work practices, and/or personal protective devices.

  8. Protease activity of PprI facilitates DNA damage response: Mn2+-dependence and substrate sequence-specificity of the proteolytic reaction.

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    Yunguang Wang

    Full Text Available The extremophilic bacterium Deinococcus radiodurans exhibits an extraordinary resistance to ionizing radiation. Previous studies established that a protein named PprI, which exists only in the Deinococcus-Thermus family, acts as a general switch to orchestrate the expression of a number of DNA damage response (DDR proteins involved in cellular radio-resistance. Here we show that the regulatory mechanism of PprI depends on its Mn(2+-dependent protease activity toward DdrO, a transcription factor that suppresses DDR genes' expression. Recognition sequence-specificity around the PprI cleavage site is essential for DNA damage repair in vivo. PprI and DdrO mediate a novel DNA damage response pathway differing from the classic LexA-mediated SOS response system found in radiation-sensitive bacterium Escherichia coli. This PprI-mediated pathway in D. radiodurans is indispensable for its extreme radio-resistance and therefore its elucidation significantly advances our understanding of the DNA damage repair mechanism in this amazing organism.

  9. Risk factors causing evolvement of alimentary-dependent diseases in specific groups of workers employed at metallurgy production and prevention meausres development

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    Yu.V. Danilova

    2017-03-01

    Full Text Available The article gives the results of hygienic and epidemiologic research of morbidity, nutrition structure, food stuffs safety, working conditions, and actual nutrition of workers employed at metallurgy productions. The research was carried out at "Magnitogorskiy metallurgy plant" PLC. 1208 steel workers and founders made up the main group. Average age of research participants amounted to 40.0 ± 0.75. The sampling was representative. We studied actual nutrition over 2010–2015 via analyzing food consumption frequency and applying extended base of food stuffs chemical structure and analyzing menus with lists of dishes offered for an organized group nutrition. We assessed both qualitative and quantitative parameters, including consumption of basic nutrients, energy, irreplaceable amino acids, lipids, vitamins, dietary fiber, essential and conditionally essential microbiological elements (60 nutrients totally, allowing for losses on a product peeling, edible contents, and other losses occurring at various treatments during cooking. We also assessed nutrition regime and other nutrition features. We detected that ratio between proteins, fats and carbohydrates was the evidence of mostly fat nutrition type. Workers were found to consume insufficient quantity of certain vitamins (A, D, and folic acid and biological elements (calcium, but they instead consumed excessive quantities of saturated fats and common salt. It is shown that actual nutrition of specific workers' groups at metallurgy production is not rational, imbalanced, and doesn't satisfy body needs causing risks of nutrition state shifts and alimentary-dependent diseases evolvement. Alimentary-dependent diseases on average amounted to 21.6 % in the total morbidity structure in 2010–2015. 10.0 % of all diseases with temporary working disability are diseases determined by mostly nutrition factor. Epidemiologic analysis of morbidity comprising diseases related to non-rational nutrition enabled us

  10. Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

    Science.gov (United States)

    Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

    2015-02-01

    Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Dysfunctional BLK in common variable immunodeficiency perturbs B-cell proliferation and ability to elicit antigen-specific CD4+ T-cell help

    NARCIS (Netherlands)

    Compeer, E.B.; Janssen, Willemijn; van Royen-Kerkhof, A; van Gijn, Marielle; van Montfrans, JM; Boes, Marianne

    2015-01-01

    Common Variable Immunodeficiency (CVID) is the most prevalent primary antibody deficiency, and characterized by defective generation of high-affinity antibodies. Patients have therefore increased risk to recurrent infections of the respiratory and intestinal tract. Development of high-affinity

  12. Antibody-dependent NK cell activation is associated with late kidney allograft dysfunction and the complement-independent alloreactive potential of donor-specific antibodies

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    Tristan Legris

    2016-08-01

    Full Text Available Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs. The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK cells as innate immune effectors of antibody-dependent cellular cytotoxicity, but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1+ cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years. Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate (eGFR over a 1-year period (hazard ratio: 2.83. In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration

  13. PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfide-dependent interactions in the endoplasmic reticulum.

    Science.gov (United States)

    van Lith, Marcel; Hartigan, Nichola; Hatch, Jennifer; Benham, Adam M

    2005-01-14

    Protein disulfide isomerase (PDI) is the archetypal enzyme involved in the formation and reshuffling of disulfide bonds in the endoplasmic reticulum (ER). PDI achieves its redox function through two highly conserved thioredoxin domains, and PDI can also operate as an ER chaperone. The substrate specificities and the exact functions of most other PDI family proteins remain important unsolved questions in biology. Here, we characterize a new and striking member of the PDI family, which we have named protein disulfide isomerase-like protein of the testis (PDILT). PDILT is the first eukaryotic SXXC protein to be characterized in the ER. Our experiments have unveiled a novel, glycosylated PDI-like protein whose tissue-specific expression and unusual motifs have implications for the evolution, catalytic function, and substrate selection of thioredoxin family proteins. We show that PDILT is an ER resident glycoprotein that liaises with partner proteins in disulfide-dependent complexes within the testis. PDILT interacts with the oxidoreductase Ero1alpha, demonstrating that the N-terminal cysteine of the CXXC sequence is not required for binding of PDI family proteins to ER oxidoreductases. The expression of PDILT, in addition to PDI in the testis, suggests that PDILT performs a specialized chaperone function in testicular cells. PDILT is an unusual PDI relative that highlights the adaptability of chaperone and redox function in enzymes of the endoplasmic reticulum.

  14. Haematopoietic depletion in vaccine-induced neonatal pancytopenia depends on both the titre and specificity of alloantibody and levels of MHC I expression.

    Science.gov (United States)

    Bell, Charlotte R; MacHugh, Niall D; Connelley, Timothy K; Degnan, Kathryn; Morrison, W Ivan

    2015-07-09

    Bovine Neonatal Pancytopenia (BNP) is a disease of calves characterised by haematopoietic depletion, mediated by ingestion of alloantibodies in colostrum. It has been linked epidemiologically to vaccination of the dams of affected calves with a particular vaccine (Pregsure) containing a novel adjuvant. Evidence suggests that BNP-alloantibodies are directed against MHC I molecules, induced by contaminant bovine cellular material from Madin-Darby Bovine Kidney (MDBK) cells used in the vaccine's production. We aimed to investigate the specificity of BNP-alloantibody for bovine MHC I alleles, particularly those expressed by MDBK cells, and whether depletion of particular cell types is due to differential MHC I expression levels. A complement-mediated cytotoxicity assay was used to assess functional serum alloantibody titres in BNP-dams, Pregsure-vaccinated dams with healthy calves, cows vaccinated with an alternative product and unvaccinated controls. Alloantibody specificity was investigated using transfected mouse lines expressing the individual MHC I alleles identified from MDBK cells and MHC I-defined bovine leukocyte lines. All BNP-dams and 50% of Pregsure-vaccinated cows were shown to have MDBK-MHC I specific alloantibodies, which cross-reacted to varying degrees with other MHC I genotypes. MHC I expression levels on different blood cell types, assessed by flow cytometry, were found to correlate with levels of alloantibody-mediated damage in vitro and in vivo. Alloantibody-killed bone marrow cells were shown to express higher levels of MHC I than undamaged cells. The results provide evidence that MHC I-specific alloantibodies play a dominant role in the pathogenesis of BNP. Haematopoietic depletion was shown to be dependent on the titre and specificity of alloantibody produced by individual cows and the density of surface MHC I expression by different cell types. Collectively, the results support the hypothesis that MHC I molecules originating from MDBK cells

  15. Efficient genome editing in hematopoietic stem cells with helper-dependent Ad5/35 vectors expressing site-specific endonucleases under microRNA regulation

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    Kamola Saydaminova

    Full Text Available Genome editing with site-specific endonucleases has implications for basic biomedical research as well as for gene therapy. We generated helper-dependent, capsid-modified adenovirus (HD-Ad5/35 vectors for zinc-finger nuclease (ZFN– or transcription activator-like effector nuclease (TALEN–mediated genome editing in human CD34+ hematopoietic stem cells (HSCs from mobilized adult donors. The production of these vectors required that ZFN and TALEN expression in HD-Ad5/35 producer 293-Cre cells was suppressed. To do this, we developed a microRNA (miRNA-based system for regulation of gene expression based on miRNA expression profiling of 293-Cre and CD34+ cells. Using miR-183-5p and miR-218-5p based regulation of transgene gene expression, we first produced an HD-Ad5/35 vector expressing a ZFN specific to the HIV coreceptor gene ccr5. We demonstrated that HD-Ad5/35.ZFNmiR vector conferred ccr5 knock out in primitive HSC (i.e., long-term culture initiating cells and NOD/SCID repopulating cells. The ccr5 gene disruption frequency achieved in engrafted HSCs found in the bone marrow of transplanted mice is clinically relevant for HIV therapy considering that these cells can give rise to multiple lineages, including all the lineages that represent targets and reservoirs for HIV. We produced a second HD-Ad5/35 vector expressing a TALEN targeting the DNase hypersensitivity region 2 (HS2 within the globin locus control region. This vector has potential for targeted gene correction in hemoglobinopathies. The miRNA regulated HD-Ad5/35 vector platform for expression of site-specific endonucleases has numerous advantages over currently used vectors as a tool for genome engineering of HSCs for therapeutic purposes.

  16. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp transcription factors

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    Pathi Satya

    2011-08-01

    Full Text Available Abstract Background Betulinic acid (BA inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS, ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.

  17. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

    International Nuclear Information System (INIS)

    Chintharlapalli, Sudhakar; Papineni, Sabitha; Lei, Ping; Pathi, Satya; Safe, Stephen

    2011-01-01

    Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent

  18. VARIABILITY IN LEVELS OF LOW-DENSITY LIPOPROTEINS CHOLESTEROL IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA DEPENDING ON AGE AND SEX AND ITS IMPORTANCE IN THE DIAGNOSIS OF THIS DISEASE

    Directory of Open Access Journals (Sweden)

    V. А. Korneva

    2017-01-01

    Full Text Available Aim. To study the ranges of low density lipoprotein (LDL cholesterol depending on the age and gender of patients with familial hypercholesterolemia (FHC by an example of a sample of patients living in the Republic of Karelia.Material and methods. Parameters of lipid spectrum of 219 patients (aged 52.5±1.7 years; males 38.3% with heterozygous FHC were studied before the start of statin therapy. Definite FHC was diagnosed in 102 patients. Lipid profile was estimated by enzymatic calorimetric method. The diagnosis of FHC was established according to the criteria of The Dutch Lipid Clinic Network.  Genetic analysis was performed in 102 patients (46.6%; pathogenic mutation in the LDL receptor was identified in 21 patients. The control group consisted of 539 people with the excluded diagnosis of FHC (aged 46.8±0.8 years; males 53.8%.Results. We determined the level of LDL cholesterol (LDLC associated with increased frequency of mutations of the LDL receptor in patients with definite FHC; mutation frequency was 3 times higher when LDLC level was more than 6.5 mmol/L. We revealed the following characteristic intervals of the LDLC levels in patients with a definite FHC: up to 20 years old – 4.8-6.2 mmol/l; in patients of 20-29 years old – 5.9-8.2 mmol/l; in the age range of 30-39 years the upper value of the LDLC levels reached 9.6 mmol/l; in individuals of 40-49 years old a stabilization, "plateau", was observed – LDLC level did not differ significantly compared to the previous decade, and was 5.4-9.0 mmol/l. In the age range  of 50-59 years the upper LDLC level was up to 11.4 mmol/l. Similar indicators were identified in patients aged 60-69 years. Patients older than 70 years with a definite FHC an upper level of LDLC was higher and reached 12.5 mmol/l. Tendency to increase in the characteristic values of LDLC with age was observed both in men and in women. Specific age-related trends  for men (an increase from a plateau by the age of 50

  19. Adjusting the specificity of an engine map based on the sensitivity of an engine control parameter relative to a performance variable

    Science.gov (United States)

    Jiang, Li; Lee, Donghoon; Yilmaz, Hakan; Stefanopoulou, Anna

    2014-10-28

    Methods and systems for engine control optimization are provided. A first and a second operating condition of a vehicle engine are detected. An initial value is identified for a first and a second engine control parameter corresponding to a combination of the detected operating conditions according to a first and a second engine map look-up table. The initial values for the engine control parameters are adjusted based on a detected engine performance variable to cause the engine performance variable to approach a target value. A first and a second sensitivity of the engine performance variable are determined in response to changes in the engine control parameters. The first engine map look-up table is adjusted when the first sensitivity is greater than a threshold, and the second engine map look-up table is adjusted when the second sensitivity is greater than a threshold.

  20. Mycobacterium tuberculosis UvrB Is a Robust DNA-Stimulated ATPase That Also Possesses Structure-Specific ATP-Dependent DNA Helicase Activity.

    Science.gov (United States)

    Thakur, Manoj; Kumar, Mohan B J; Muniyappa, K

    2016-10-18

    Much is known about the Escherichia coli nucleotide excision repair (NER) pathway; however, very little is understood about the proteins involved and the molecular mechanism of NER in mycobacteria. In this study, we show that Mycobacterium tuberculosis UvrB (MtUvrB), which exists in solution as a monomer, binds to DNA in a structure-dependent manner. A systematic examination of MtUvrB substrate specificity reveals that it associates preferentially with single-stranded DNA, duplexes with 3' or 5' overhangs, and linear duplex DNA with splayed arms. Whereas E. coli UvrB (EcUvrB) binds weakly to undamaged DNA and has no ATPase activity, MtUvrB possesses intrinsic ATPase activity that is greatly stimulated by both single- and double-stranded DNA. Strikingly, we found that MtUvrB, but not EcUvrB, possesses the DNA unwinding activity characteristic of an ATP-dependent DNA helicase. The helicase activity of MtUvrB proceeds in the 3' to 5' direction and is strongly modulated by a nontranslocating 5' single-stranded tail, indicating that in addition to the translocating strand it also interacts with the 5' end of the substrate. The fraction of DNA unwound by MtUvrB decreases significantly as the length of the duplex increases: it fails to unwind duplexes longer than 70 bp. These results, on one hand, reveal significant mechanistic differences between MtUvrB and EcUvrB and, on the other, support an alternative role for UvrB in the processing of key DNA replication intermediates. Altogether, our findings provide insights into the catalytic functions of UvrB and lay the foundation for further understanding of the NER pathway in M. tuberculosis.

  1. Antitumor activity of chLpMab-2, a human-mouse chimeric cancer-specific antihuman podoplanin antibody, via antibody-dependent cellular cytotoxicity.

    Science.gov (United States)

    Kaneko, Mika K; Yamada, Shinji; Nakamura, Takuro; Abe, Shinji; Nishioka, Yasuhiko; Kunita, Akiko; Fukayama, Masashi; Fujii, Yuki; Ogasawara, Satoshi; Kato, Yukinari

    2017-04-01

    Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology. In this study we developed chLpMab-2, a human-mouse chimeric anti-hPDPN antibody, derived from LpMab-2. chLpMab-2 was produced using fucosyltransferase 8-knockout (KO) Chinese hamster ovary (CHO)-S cell lines. By flow cytometry, chLpMab-2 reacted with hPDPN-expressing cancer cell lines including glioblastomas, mesotheliomas, and lung cancers. However, it showed low reaction with normal cell lines such as lymphatic endothelial and renal epithelial cells. Moreover, chLpMab-2 exhibited high antibody-dependent cellular cytotoxicity (ADCC) against PDPN-expressing cells, despite its low complement-dependent cytotoxicity. Furthermore, treatment with chLpMab-2 abolished tumor growth in xenograft models of CHO/hPDPN, indicating that chLpMab-2 suppressed tumor development via ADCC. In conclusion, chLpMab-2 could be useful as a novel antibody-based therapy against hPDPN-expressing tumors. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. Development and Validation of Culture-Specific Variable Response Inconsistency and True Response Inconsistency Scales for Use with the Korean MMPI-2

    Science.gov (United States)

    Ketterer, Holly L.; Han, Kyunghee; Hur, Jaehong; Moon, Kyungjoo

    2010-01-01

    In response to the concern that Minnesota Multiphasic Personality Inventory-2 (MMPI-2; J. N. Butcher, W. Dahlstrom, J. R. Graham, A. Tellegen, & B. Kaemmer, 1989; J. N. Butcher et al., 2001) Variable Response Inconsistency (VRIN) and True Response Inconsistency (TRIN) score invalidity criteria recommended for use with American samples results…

  3. Reduction in camera-specific variability in [(123)I]FP-CIT SPECT outcome measures by image reconstruction optimized for multisite settings

    DEFF Research Database (Denmark)

    Buchert, Ralph; Kluge, Andreas; Tossici-Bolt, Livia

    2016-01-01

    the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure. RESULTS: The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2...... as the reference provides more stable quantitative estimates than occipital or cerebellar binding....

  4. Propeptides are sufficient to regulate organelle-specific pH-dependent activation of furin and proprotein convertase 1/3.

    Science.gov (United States)

    Dillon, Stephanie L; Williamson, Danielle M; Elferich, Johannes; Radler, David; Joshi, Rajendra; Thomas, Gary; Shinde, Ujwal

    2012-10-12

    The proprotein convertases (PCs) furin and proprotein convertase 1/3 (PC1) cleave substrates at dibasic residues along the eukaryotic secretory/endocytic pathway. PCs are evolutionarily related to bacterial subtilisin and are synthesized as zymogens. They contain N-terminal propeptides (PRO) that function as dedicated catalysts that facilitate folding and regulate activation of cognate proteases through multiple-ordered cleavages. Previous studies identified a histidine residue (His69) that functions as a pH sensor in the propeptide of furin (PRO(FUR)), which regulates furin activation at pH~6.5 within the trans-Golgi network. Although this residue is conserved in the PC1 propeptide (PRO(PC1)), PC1 nonetheless activates at pH~5.5 within the dense core secretory granules. Here, we analyze the mechanism by which PRO(FUR) regulates furin activation and examine why PRO(FUR) and PRO(PC1) differ in their pH-dependent activation. Sequence analyses establish that while both PRO(FUR) and PRO(PC1) are enriched in histidines when compared with cognate catalytic domains and prokaryotic orthologs, histidine content in PRO(FUR) is ~2-fold greater than that in PRO(PC1), which may augment its pH sensitivity. Spectroscopy and molecular dynamics establish that histidine protonation significantly unfolds PRO(FUR) when compared to PRO(PC1) to enhance autoproteolysis. We further demonstrate that PRO(FUR) and PRO(PC1) are sufficient to confer organelle sensing on folding and activation of their cognate proteases. Swapping propeptides between furin and PC1 transfers pH-dependent protease activation in a propeptide-dictated manner in vitro and in cells. Since prokaryotes lack organelles and eukaryotic PCs evolved from propeptide-dependent, not propeptide-independent prokaryotic subtilases, our results suggest that histidine enrichment may have enabled propeptides to evolve to exploit pH gradients to activate within specific organelles. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Substrate specificity of flavin-dependent vanillyl-alcohol oxidase from Penicillium simplicissimum. Evidence for the production of 4-hydroxycinnamyl alcohols from 4-allylphenols.

    Science.gov (United States)

    Fraaije, M W; Veeger, C; van Berkel, W J

    1995-11-15

    The substrate specificity of the flavoprotein vanillyl-alcohol oxidase from Penicillium simplicissimum was investigated. Vanillyl-alcohol oxidase catalyzes besides the oxidation of 4-hydroxybenzyl alcohols, the oxidative deamination of 4-hydroxybenzylamines and the oxidative demethylation of 4-(methoxymethyl)phenols. During the conversion of vanillylamine to vanillin, a transient intermediate, most probably vanillylimine, is observed. Vanillyl-alcohol oxidase weakly in